Circulating PCSK9 binds to the extracellular domain of LDLR, and then mediates the internalization and lysosomal degradation of LDLR, which leads to the lower clearance of LDL cholesterol (LDL-C) from the bloodstream and thus results in hypercholesterolemia [5]. The gene discussed is LDLR; the disease is familial hypercholesterolemia.