Zinc metalloprotease that mediates intramembrane proteolysis of proteins such as ATF6， ATF6B， SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:11163209， PubMed:10805775).Catalyzes the second step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment， thereby releasing the N-terminal segment with a portion of the transmembrane segment attached (PubMed:10805775， PubMed:27380894， PubMed:9659902).Mature N-terminal SREBP fragments shuttle to the nucleus and activate gene transcription (PubMed:10805775， PubMed:27380894， PubMed:9659902).Also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) (PubMed:11163209).Involved in intramembrane proteolysis during bone formation (PubMed:27380894).In astrocytes and osteoblasts， upon DNA damage and ER stress， mediates the second step of the regulated intramembrane proteolyt