The Low-density lipoprotein receptor (LDLR) binds LDL, the major cholesterol-carrying lipoprotein of plasma, on the cell surface in clathrin-coated pits, followed by endocytosis. LDLR defects lead to familial hypercholesterolemia (FH), a common autosomal semi-dominant disease affecting 1 in 500 individuals and characterized by cholesterol deposit in the skin, tendons, and coronary arteries (atherosclerosis). LDLR acts as a receptor for the HIV-1 Tat protein in neurons and mediates its internalization.