Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20C (PubMed:10644685, PubMed:12782636, PubMed:21719679, PubMed:34349020). Cleaves substrates after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu (PubMed:10644685, PubMed:21719679). Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:12782636). Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) (PubMed:12782636). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes (PubMed:21719679). Cleaves the propeptide from FAM20C which is required for FAM20C secretion from the Golgi apparatus membrane and for enhancement of FAM20C kinase activity, promoting osteoblast differentiation and biomineralization (PubMed:34349020). Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes (PubMed:21719679, PubMed:30046013). It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation (PubMed:30046013). Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking (PubMed:30046013). Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3. Inhibited by divalent copper and zinc ions, but not by nickel or cobalt (PubMed:10644685). Inhibited by its prosegment, but not smaller fragments thereof (PubMed:10644685). Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor (PubMed:12782636). May sort to other organelles, including lysosomal and/or endosomal compartments. Widely expressed. Down-regulated by sterols. The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and late into a secreted 98 kDa form (PubMed:10644685). The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates (PubMed:10644685). The disease is caused by variants affecting the gene represented in this entry. Belongs to the peptidase S8 family.