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LDLR / Low-density lipoprotein receptor · IHC design guide
Design Immunohistochemistry for LDLR
Plan LDLR IHC using the cytoplasmic tissue pattern reported by HPA, including high staining in testis Leydig cells (HPA tissue IHC). Interpret that pattern alongside LDLR’s cell membrane and endosomal locations and its rapid internalization after ligand binding (UniProt).
Evidence assembled Oct 2026 · For research use; verify linked source records and product datasheet before use
LDLR Immunohistochemistry Experimental Design Guide
Expected localisation, validated protocols, controls and antibodies — the at-a-glance facts below, then the full design guide.
Must know before staining
| Expected localisation | Cytoplasmic staining in several tissues (HPA tissue IHC) | |
| Staining pattern | Cytoplasmic staining; high in testis Leydig cells (HPA tissue IHC) | |
| Antigen retrieval | EDTA pH 8.0 HIER, heat-mediated (datasheet A00076-2) | |
| Positive control | Testis+4 more · see all | |
| Negative control | Adipose tissue+4 more · see all |
Important caveats
Reasons your staining may differ from the expected pattern.
| Fixation | Keep fixation consistent across sections (standard IHC practice; not target-specific); Matched tissue-IHC evidence does not establish the fixation claim. Validate the specimen-specific method before use. (selected-SKU IHC image A00076-2) | |
| Caveat | Ligand binding rapidly internalizes LDLR (UniProt) | |
| Regulation | Expression regulation is not annotated (UniProt) | |
| Isoform / epitope | 6 isoforms; check extracellular versus cytoplasmic epitope (UniProt) |
Section 1
Recommended LDLR IHC & IF Protocols
Compare the catalog antibody’s IHC protocol (datasheet: A00076-2) with four published LDLR chromogenic IHC protocols (PMC8664653; PMC9958636; PMC6413123; PMC5391547).
| Sample | Paraffin-embedded human liver cancer tissue; fixative not specified (datasheet A00076-2) |
| Fixation | Image fixative and duration unreported (datasheet A00076-2); verify before use. |
| Sectioning | 4–5 µm sections on charged slides (standard) |
| Deparaffinisation | Xylene, graded ethanol series to water (standard) |
| Antigen retrieval | Heat retrieval: EDTA pH 8.0 (datasheet A00076-2); 20 min, 95–100 °C (standard) |
| Peroxidase block | 3% H2O2, 10 min, room temperature (standard) |
| Blocking | 10% goat serum (datasheet A00076-2) |
| Primary antibody | Rabbit anti-LDLR, 0.5-1μg/ml (datasheet A00076-2) |
| Primary incubation | Overnight at 4 °C (datasheet A00076-2) |
| Detection | Streptavidin-biotin complex (SABC), DAB chromogen (datasheet A00076-2) |
| Counterstain | Hematoxylin, blue, dehydrate and mount (standard) |
| Expected result | LDLR-positive staining in leydig cells of testis (HPA tissue IHC: High). HPA tissue profile: Cytoplasmic expression in several tissues. No signal in the no-primary control. |
💡Decision noteStart with heat-mediated EDTA retrieval at pH 8.0 for the catalog antibody (datasheet: A00076-2); a published LDLR IHC protocol also used EDTA at pH 8.0 (PMC5391547).
Section 2
What Is the Expected LDLR Staining Pattern?
LDLR is a cell-surface receptor that also occupies coated pits, Golgi and endolysosomal compartments (UniProt P01130 subcellular location). In tissue IHC, expect chiefly cytoplasmic staining, strongest in testicular Leydig cells and moderate in several glandular and other cell types (HPA: tissue IHC). Its extracellular region spans residues 22–788, followed by a transmembrane segment and cytoplasmic tail (UniProt P01130 topology). HPA rates the tissue staining Approved, while reporting low consistency with RNA expression (HPA: tissue IHC reliability).
| Strong Leydig-cell staining, or moderate staining in hepatocytes, adrenal or intestinal glandular cells, or kidney tubules (HPA: tissue IHC). | These match the reported cell types and levels: Leydig cells are High; the other listed populations are Medium (HPA: tissue IHC). Assess the cellular pattern alongside the tissue control because HPA reports low staining–RNA consistency (HPA: tissue IHC reliability). |
| Cytoplasmic or punctate signal, with some cell-edge staining, in an expected positive cell (HPA: cytoplasmic tissue profile; UniProt P01130 subcellular location). | This is compatible with a receptor that cycles through the surface and intracellular compartments after ligand binding (UniProt P01130 subcellular location and function). Puncta alone do not identify a particular organelle; HPA identifies vesicles in ICC-IF (HPA: subcellular). |
| A dominant nuclear-only signal in cells being scored for LDLR. | Treat it as a possible staining artefact: the supplied location records identify membrane and intracellular vesicular compartments, without a nuclear assignment (UniProt P01130 subcellular location; HPA: subcellular). Check a positive-tissue control and a no-primary control before interpreting it as LDLR (standard IHC practice). |
| Strong staining in adipocytes or appendix glandular cells, while expected positive cells are unstained. | Those populations are Not detected in the HPA tissue panel (HPA: adipocytes; HPA: appendix glandular cells). The mismatch raises concern for off-target staining or endogenous detection activity; a single section cannot distinguish the two (standard IHC practice). |
| Diffuse chromogen across tissue and empty spaces, obscuring cell boundaries. | This does not support a cell-specific LDLR call. Compare a no-primary section to locate detection-system background, then assess whether expected Leydig-cell or hepatocyte staining remains distinguishable (standard IHC practice; HPA: tissue IHC). |
💡Expected LDLR appearanceCall a positive result when LDLR staining is cell-associated and mainly cytoplasmic, possibly with a cell-edge component, in High Leydig cells or Medium hepatocytes and other listed positive populations; broad background or nuclear-only staining is suspect (HPA: tissue IHC; UniProt P01130 subcellular location).
| Compartment and receptor movement (UniProt P01130 subcellular location and function). | LDLR occupies the plasma membrane, coated pits, Golgi and endolysosomal compartments and is rapidly endocytosed after ligand binding. Interpret cell-edge and intracellular staining together rather than requiring one exclusive compartment (UniProt P01130 subcellular location and function). |
| Epitope location and processing (UniProt P01130 topology and processing). | The mature chain is residues 22–860, with an extracellular region at 22–788 and cytoplasmic tail at 811–860 (UniProt P01130 topology and processing). The supplied record does not locate the catalog antibody's epitope, so it cannot predict which compartment or retrieval condition that antibody favors. |
| Tissue benchmark and validation (HPA: tissue IHC; HPA: antibodies). | Use the named positive and Not detected cell populations as comparison points. HPA calls tissue staining Approved but notes low consistency with RNA; its listed IHC antibodies are Approved, not Enhanced (HPA: tissue IHC reliability; HPA: antibodies). |
| IF/ICC: what should appear? | Vesicles are the approved main location in HPA ICC-IF, with images from EFO-21, GAMG and U2OS (HPA: subcellular). That supports a vesicular IF interpretation; it does not establish an IHC retrieval setting or an IF protocol for this guide. |
| Fixation and retrieval evidence. | Target-specific fixation sensitivity and an LDLR retrieval condition are unreported in the supplied UniProt and HPA records. Assess retrieval changes against the same positive and negative controls as a general IHC optimization step (standard IHC practice). |
| Situation | Likely cause | Next action |
|---|---|---|
| No signal in Leydig cells or hepatocytes, including the positive control (HPA: tissue IHC). | The run may have failed at retrieval, antibody incubation or detection; the supplied sources do not identify an LDLR-specific failure point. | Check section integrity and detection controls, then optimize retrieval and antibody concentration under the laboratory's IHC workflow (standard IHC practice). Do not infer absent LDLR from a failed positive control. |
| Only nuclei stain, with no cell-associated cytoplasmic or edge signal. | A nuclear-only pattern conflicts with the supplied LDLR location records (UniProt P01130 subcellular location; HPA: subcellular). | Review the no-primary section, chromogen deposition and counterstain, then compare a known positive cell population before scoring the run (standard IHC practice; HPA: tissue IHC). |
| Adipocytes or appendix glandular cells stain more strongly than the expected positive population. | HPA reports those cells as Not detected, so off-target binding or endogenous detection activity is plausible (HPA: tissue IHC; standard IHC practice). | Compare no-primary and positive-tissue controls; address endogenous detection activity if the control reveals it, and re-evaluate antibody specificity (standard IHC practice). |
| Background is diffuse and the boundaries of positive cells cannot be resolved. | Non-specific antibody or detection signal may obscure the cell-specific pattern (standard IHC practice). | Compare no-primary staining, review blocking and antibody concentration, and score only interpretable cells against a tissue control (standard IHC practice; HPA: tissue IHC). |
| A positive tissue stains, but intensity differs from the HPA example. | HPA reports low consistency between antibody staining and RNA expression, and levels vary by cell population (HPA: tissue IHC reliability and levels). | Compare the same cell type and compartment across sections; use the HPA level as a benchmark, not a quantitative cutoff (HPA: tissue IHC; standard IHC practice). |
| An IF image shows puncta but little visible cell-surface signal. | HPA's approved ICC-IF location is vesicles, while UniProt also places LDLR at the membrane and in trafficking compartments (HPA: subcellular; UniProt P01130 subcellular location). | Interpret puncta with a cellular counterstain and appropriate IF controls; avoid rejecting the image solely for weak edge signal (standard IF practice; HPA: subcellular). |
Experiment evidence
IHC & IF images showing LDLR staining
A00076-2 · IHCIHC analysis of LDLR using anti-LDLR antibody (A00076-2). LDLR was detected in paraffin-embedded section of human liver cancer tissue. Heat
A00076-2 · IHCIHC analysis of LDLR using anti-LDLR antibody (A00076-2). LDLR was detected in paraffin-embedded section of human rectal cancer tissue. Heat
A00076 · IHCImmunohistochemistry of LDL-R in human liver tissue with LDL-R antibody at 2.5 μg/mL.
A00076 · IFImmunofluorescence of LDLR in human liver tissue with LDLR antibody at 20 μg/mL.
M00076 · IHCImmunohistochemical analysis of paraffin-embedded human liver carcinoma, using LDL Receptor Antibody .
HPA · Cerebral cortexHuman Protein Atlas IHC, Cerebral cortex. Source: https://www.proteinatlas.org/ENSG00000130164-LDLR/tissue/cerebral+cortex#imid_2815896
HPA · StomachHuman Protein Atlas IHC, Stomach. Source: https://www.proteinatlas.org/ENSG00000130164-LDLR/tissue/stomach+1#imid_2815812
HPA · ColonHuman Protein Atlas IHC, Colon. Source: https://www.proteinatlas.org/ENSG00000130164-LDLR/tissue/colon#imid_2815838
HPA · LiverHuman Protein Atlas IHC, Liver. Source: https://www.proteinatlas.org/ENSG00000130164-LDLR/tissue/liver#imid_2815831
HPA · ICC-IF EFO-21Human Protein Atlas immunofluorescence, EFO-21, antibody HPA009974; green = LDLR, blue = nucleus, red = microtubules.
HPA · ICC-IF EFO-21Human Protein Atlas immunofluorescence, EFO-21, antibody HPA009974; green = LDLR, blue = nucleus, red = microtubules.
← swipe / scroll for more images →
Real IHC / IF data behind the staining-pattern expectations in this section.
Sample controls for LDLR IHC & IF
🧪Run testis first and look for staining in Leydig cells (HPA: High in testis Leydig cells). Use adipose tissue as the negative tissue, assessing adipocytes for background staining (HPA: Not detected in adipocytes). On the testis slide, non-Leydig cells without convincing LDLR staining can serve as internal background comparators; the HPA row does not establish that every other testicular cell is negative (HPA: High in Leydig cells).
Positive control tissue: Testis (Leydig cells, HPA High)
Negative control tissue: Adipose tissue (HPA Not detected)
ICC-IF cell lines (HPA subcellular resource): HPA ICC-IF images show LDLR in EFO-21, GAMG, U2OS, with annotated localisation: Vesicles (approved) (HPA subcellular).
Technical controls: Include a no-primary, secondary-only control and nonimmune rabbit IgG matched to the primary antibody’s clonality where known (caption: rabbit anti-LDLR primary). Use LDLR knockout material as a biological negative; assess endogenous peroxidase and biotin before interpreting the testis signal (caption: biotinylated secondary, SABC and DAB).
⚠️Feasibility: A target-specific fixation window or fixation effect is unreported, and the selected A00076-2 paraffin-section caption does not state the fixative. The reported IHC procedure uses heat retrieval in EDTA at pH 8.0 (caption: heat-mediated EDTA retrieval); whether frozen sections or IF would be easier is unreported. In testis, distinguish DAB staining from any intrinsic brown pigment by inspecting the control slide (caption: DAB detection).
HPA tissue IHC evidence for LDLR
Comprehensive Human Protein Atlas IHC scoring per tissue (reliability: Approved — Low consistency between antibody staining and RNA expression data.). Rows are taken directly from the HPA tissue chart — click any row's HPA link to view the source.
Positive expression · recommended positive controls
| Tissue | Cell type | Level | Evidence | Source |
|---|---|---|---|---|
| Testis | Leydig cells | High | Protein (IHC) | HPA → |
| Adrenal gland | Glandular cells | Medium | Protein (IHC) | HPA → |
| Colon | Glandular cells | Medium | Protein (IHC) | HPA → |
| Duodenum | Glandular cells | Medium | Protein (IHC) | HPA → |
| Kidney | Cells in tubules | Medium | Protein (IHC) | HPA → |
Undetected expression · recommended negative controls
| Tissue | Cell type | Level | Evidence | Source |
|---|---|---|---|---|
| Adipose tissue | Adipocytes | Not detected | Protein (IHC) | HPA → |
| Appendix | Glandular cells | Not detected | Protein (IHC) | HPA → |
| Bone marrow | Hematopoietic cells | Not detected | Protein (IHC) | HPA → |
| Bronchus | Respiratory epithelial cells | Not detected | Protein (IHC) | HPA → |
| Cervix | Glandular cells | Not detected | Protein (IHC) | HPA → |
Section 3
Advanced LDLR IHC Tips
Use compartment, cell type and matched controls to assess LDLR staining in paraffin sections.
Which retrieval condition should I start with for LDLR in paraffin sections?
Start with heat-mediated retrieval in EDTA pH 8.0 for the catalog antibody (datasheet A00076-2). The selected paraffin-section image used this retrieval before 1 μg/ml primary antibody overnight at 4°C; its fixative was not reported (caption A00076-2). If staining is weak, compare heating durations on matched sections while keeping antibody concentration, detection and development constant (standard IHC practice). Assess improvement in hepatocytes alongside background in adipocytes, since the tissue atlas reports medium hepatocyte staining and no detected adipocyte staining (HPA tissue IHC).
Could fixation explain weak or patchy LDLR staining?
Target-specific fixation sensitivity is unknown: the selected paraffin-section caption does not state a fixative (caption A00076-2). Record the actual fixative, fixation duration and processing history for each specimen before comparing staining across cases (standard IHC practice). If weak staining tracks a processing batch, repeat staining on matched sections with the same EDTA pH 8.0 retrieval and 1 μg/ml primary concentration used in the selected image (caption A00076-2). Include a tissue control in each run and evaluate whether signal and morphology change together, without attributing any difference to LDLR-specific fixation effects (standard IHC practice).
Should LDLR staining be membranous, cytoplasmic or both?
LDLR can appear at the cell surface and in intracellular trafficking compartments: its annotated locations include coated pits, Golgi, endosomes and lysosomes (UniProt P01130 subcellular location). Its extracellular region spans residues 22–788, followed by a transmembrane segment at 789–810 and a cytoplasmic tail at 811–860 (UniProt P01130 topology). The tissue atlas describes cytoplasmic staining in several tissues, while its cell imaging summary identifies vesicles (HPA tissue IHC; HPA subcellular). Score membrane-associated and punctate cytoplasmic signal separately, using tissue architecture and a no-primary control to assess whether diffuse staining reflects background (standard IHC practice).
How can epitope choice affect interpretation across LDLR isoforms?
LDLR has 6 annotated isoforms, so establish which sequence the catalog antibody recognizes before making isoform-specific claims (UniProt P01130 isoforms; standard IHC practice). The reference sequence contains an extracellular region at residues 22–788 and a cytoplasmic region at 811–860, but the supplied antibody caption does not identify its epitope (UniProt P01130 topology; caption A00076-2). Five annotated glycosylation sites occur at residues 97, 156, 272, 515 and 657; their presence alone does not establish an effect on staining (UniProt P01130 glycosylation). If cases differ in staining pattern, verify epitope coverage and use an independent antibody or orthogonal assay before assigning the difference to a particular isoform (standard IHC practice).
How should an IF follow-up test support the chromogenic LDLR result?
Use IF as a companion localisation check, pairing LDLR with a marker for the expected cell type, such as hepatocytes in liver sections (HPA tissue IHC; standard IF practice). Select fluorophores after checking tissue autofluorescence in unstained controls, and keep the LDLR channel spectrally distinct from the cell-marker channel (standard IF practice). Permeabilisation depends on epitope position: access to the cytoplasmic tail at residues 811–860 generally requires permeabilisation, whereas surface-accessible extracellular epitopes may be assessed without it (UniProt P01130 topology; standard IF practice). The supplied IHC caption does not specify the antibody epitope, so confirm it before using either IF condition to interpret absent signal (caption A00076-2; standard IF practice).
What should I check when LDLR DAB staining looks widespread?
First inspect a no-primary section to separate antibody-dependent staining from detection-system or tissue background (standard IHC practice). The selected image used 10% goat serum block, a biotinylated secondary, a streptavidin–biotin complex and DAB; those reagents define the tested detection sequence (caption A00076-2). In this workflow, compare a no-primary control, an appropriate secondary-only control and a peroxidase-blocked section, particularly where pigment or endogenous enzyme could resemble brown signal (standard IHC practice). Reduce overdevelopment only after controls are checked, and compare hepatocyte signal with adipocytes reported as not detected rather than assuming all cytoplasmic colour is LDLR (HPA tissue IHC; standard IHC practice).
How can I quantify LDLR staining across paraffin sections? ⚠ ANSWER MARKED FOR VERIFICATION
Define the cell population and region before scoring; for liver, hepatocytes are a documented medium-staining population (HPA tissue IHC; standard IHC practice). Report the percentage of positive target cells and staining intensity, or calculate an H-score from intensity categories 0–3, with a possible range of 0–300 (standard IHC practice). Score membrane-associated and cytoplasmic signal separately because LDLR occupies the surface and trafficking compartments, while tissue IHC often appears cytoplasmic (UniProt P01130 subcellular location; HPA tissue IHC). Normalise counts to evaluable target cells or positive-cell density to measured tissue area in mm², and hold threshold and DAB development settings constant across comparisons (standard IHC practice).
When is an apparent LDLR-positive cell likely to be an artefact?
A plausible LDLR pattern is membrane-associated or punctate cytoplasmic signal, consistent with its surface and endosomal localisation (UniProt P01130 subcellular location; HPA subcellular). Check the identified cell type: the tissue atlas reports medium staining in hepatocytes and lung macrophages, but no detected staining in adipocytes (HPA tissue IHC). Treat staining confined to section edges, necrotic areas or a no-primary control as suspect, and use a peroxidase-block control to assess enzyme-derived DAB colour (standard IHC practice). Interpret even plausible staining cautiously because the tissue atlas rates its LDLR tissue stain approved while reporting low consistency with RNA expression data (HPA tissue IHC).
Boster reagents
Best LDLR / Low-density lipoprotein receptor IHC Antibodies
Three anti-LDLR antibodies have human liver or liver carcinoma IHC images (catalog IHC captions); A00076 also has a human liver IF image (A00076 IF caption).
Real IHC data
Anti-LDL Receptor/LDLR Antibody ®
Cat # A00076-2
Real IHC data
Anti-LDL-R Antibody
Cat # A00076
Real IHC data
Anti-LDL Receptor Rabbit Monoclonal Antibody
Cat # M00076
A00076-2 shows IHC in paraffin-embedded human liver and rectal cancer sections (A00076-2 IHC captions), while A00076 shows IHC and IF in human liver tissue (A00076 image captions). M00076 shows IHC in paraffin-embedded human liver carcinoma (M00076 IHC caption).
Which to pick: For paraffin-section IHC, choose A00076-2 at 0.5–1 μg/mL (A00076-2 catalog dilution); its own captions document paraffin sections but do not report the fixative (A00076-2 IHC captions). M00076 is a rabbit monoclonal IHC alternative with a paraffin-section image; its fixative is also unreported (M00076 catalog clone and IHC caption). For tissue IF, choose A00076 at 20 μg/mL (A00076 catalog dilution and IF caption); ICC validation is unreported (A00076 applications and image captions). For broader listed species reactivity, A00076 covers human, mouse and rat, while A00076-2 covers human and rat and M00076 covers human and mouse (catalog reactivity); the supplied IHC and IF images show human tissue only (catalog image captions).
Each figure is that product's own IHC / IF validation image from its datasheet.
References
- UniProt Consortium. UniProt entry P01130 (LDLR_HUMAN, Low-density lipoprotein receptor).
- Human Protein Atlas. LDLR tissue IHC expression (reliability: Approved).
- Human Protein Atlas. LDLR subcellular location (ICC-IF): Localized to vesicles..
- Human Protein Atlas. LDLR antibody validation summary (3 antibodies).
- Low Density Lipoprotein Receptor (LDLR) and 3-Hydroxy-3-Methylglutaryl Coenzyme a Reductase (HMGCR) Expression are Associated with Platinum-Resistance and Prognosis in Ovarian Carcinoma Patients. Cancer management and research 2021 — PMC8664653.
- Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery. Pharmaceutics 2023 — PMC9958636.
- Can Carob-Fruit-Extract-Enriched Meat Improve the Lipoprotein Profile, VLDL-Oxidation, and LDL Receptor Levels Induced by an Atherogenic Diet in STZ-NAD-Diabetic Rats?. Nutrients 2019 — PMC6413123.
- Serum low-density lipoprotein and low-density lipoprotein expression level at diagnosis are favorable prognostic factors in patients with small-cell lung cancer (SCLC). BMC cancer 2017 — PMC5391547.
- PubMed PMID:6091915 — UniProt-cited evidence.
- PubMed PMID:2988123 — UniProt-cited evidence.
- PubMed PMID:14702039 — UniProt-cited evidence.
Immunohistochemistry protocol sheet for LDLR (Low-density lipoprotein receptor). Expected localisation Cytoplasmic staining in several tissues (HPA tissue IHC). Antigen retrieval: EDTA pH 8.0 HIER, heat-mediated (datasheet A00076-2). Validated IHC antibody: A00076-2 at 0.5-1μg/ml (the product's own IHC validation image is shown). Controls (HPA): positive Testis (Leydig cells); negative Adipose tissue. IHC-P workflow on paraffin sections; fixative unspecified. Protocol steps: 1. Sample: Paraffin-embedded human liver cancer tissue; fixative not specified (datasheet A00076-2); 2. Fixation: Image fixative and duration unreported (datasheet A00076-2); verify before use.; 3. Sectioning: 4–5 µm sections on charged slides (standard); 4. Deparaffinisation: Xylene, graded ethanol series to water (standard); 5. Antigen retrieval: Heat retrieval: EDTA pH 8.0 (datasheet A00076-2); 20 min, 95–100 °C (standard); 6. Peroxidase block: 3% H2O2, 10 min , room temperature (standard); 7. Blocking: 10% goat serum (datasheet A00076-2); 8. Primary antibody: Rabbit anti-LDLR, 0.5-1μg/ml (datasheet A00076-2); 9. Primary incubation: Overnight at 4 °C (datasheet A00076-2). Watch for: Fixation: Keep fixation consistent across sections (standard IHC practice; not target-specific); Matched tissue-IHC evidence does not establish the fixation claim. Validate the specimen-specific method before use. (selected-SKU IHC image A00076-2); Caveat: Ligand binding rapidly internalizes LDLR (UniProt); Isoform / epitope: 6 isoforms; check extracellular versus cytoplasmic epitope (UniProt); Regulation: Expression regulation is not annotated (UniProt). Evidence: UniProt P01130, HPA tissue IHC · Approved, HPA ICC-IF · vesicles., Datasheet A00076-2, PMC8664653, PMC9958636. QR code links to https://www.bosterbio.com/bosterbio-gene-info-cards/LDLR/immunohistochemistry-ihc-guide.