PCSK9 and Hypocholesterolemia: Notably, the PCSK9 C-terminal domain is not directly involved in PCSK9-LDLR binding [22], but human genetic analyses of FH have suggested that several gain- (H553R) or loss- (S462P and Q554E) point mutations within the C-terminal domain of PCSK9 result in hyper- or hypocholesterolemia, respectively [23–26].