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:9809072, PubMed:11163209). 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:9809072, PubMed:11163209). Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:9809072). Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) (PubMed:11163209). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes (By similarity). 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 (By similarity). Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes (By similarity). It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation (By similarity). Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking (By similarity). 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. Inhibited by its prosegment, but not smaller fragments thereof. Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor. May sort to other organelles, including lysosomal and/or endosomal compartments. 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. The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates. Belongs to the peptidase S8 family.