LDLR and Hypercholesterolemia: Loss‐of‐function mutations in PCSK9 gene induce high hepatic levels of LDLR and increased plasma LDL‐C clearance, whereas gain‐of‐function PCSK9 gene mutations and overexpression of recombinant PCSK9 reduce LDLR protein levels in the liver and cause severe hypercholesterolaemia 60, 61, 62.