Signal peptide peptidase-like 3 (Sppl3)

Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries. Acts like a sheddase by mediating the proteolytic release and secretion of active site- containing ectodomains of glycan-modifiying glycosidase and glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1 (PubMed:25354954, PubMed:25827571).

Plays a role in the regulation of cellular glycosylation processes (PubMed:25354954). Required to connect T-cell antigen receptor (TCR) and calcineurin-NFAT signaling cascades in lymphocytes by promoting the institution of STIM1 and ORAI1 during store-operated calcium entry (SOCE) in a protease- independent manner (PubMed:25384971).