PCSK9 was identified as a cause of familial hypercholesterolemia (genetically elevated blood LDL-C levels) via patients who were found to have single copies of gain-of-function mutations in the gene (32), whereas people with single copies of PCSK9 nonsense (loss-of-function) mutations have substantially reduced blood LDL-C levels as well as up to 88% reduction in risk of coronary heart disease (33) without having any serious adverse health consequences (34). Here, PCSK9 is linked to familial hypercholesterolemia.