The critical role of PCSK9 in cholesterol regulation was discovered, as its gain-of-function variants could lead to human familial hypercholesterolemia, while its nonsense mutations (Y142X and C679X) in African Americans were associated with 40% lower plasma level of low-density lipoprotein-cholesterol (LDL-C) and lower risk of coronary heart disease (CHD) (23, 24). Here, PCSK9 is linked to familial hypercholesterolemia.