PCSK9 and Hypercholesterolemia: These revelations shed light on the genetics of hypercholesterolemia and established human PCSK9 as an essential FH gene for LDL-C regulation.12 Further research into PCSK9 biosynthesis revealed that while PCSK9 also underwent autocatalytic cleavage of its prodomain in the ER, it was the only proprotein convertase (PC) that continuously remained noncovalently attached to its prodomain, even in the secreted form15,16,19,37 (Fig. 1a).