LDLR and familial hypercholesterolemia: Mutations of the LDLR gene impair LDL binding and internalization, as well as lysosomal hydrolysis, recycling and secretion, and cause hypercholesterolemia and severe familial hypercholesterolemia (FH).[21] Patients with FH have very high serum LDL cholesterol (>500 mg/dl) and premature ACVD.