In 2003, Abifadel and colleagues reported that two kindreds with premature CVD and apparently unexplained autosomal dominant hypercholesterolaemia, based on known FH genetic mutations, were affected by gain-of-function mutations in the PCSK9 gene leading to increased activity of PCSK9 and marked hypercholesterolaemia [8]. Here, PCSK9 is linked to Hypercholesterolemia.