Hypercholesterolemia can result from various factors, including gain-of-function mutations in proprotein convertase subtilisin kexin 9 (PCSK9), leading to decreased low-density lipoprotein (LDL) receptor levels, and loss-of-function variants associated with reduced LDL-cholesterol (LDL-C) levels and decreased coronary heart disease (CHD) risk [28,29,30,31]. The gene discussed is LDLR; the disease is familial hypercholesterolemia.