HMG-CoA reductase is the rate-determining enzyme for the hepatic synthesis of cholesterol, and a reduction in liver HMG-CoA reductase activity is the primary target for medical treatment of hypercholesterolaemia(82) since this will reduce the amount of endogenous cholesterol available for secretion from the liver in VLDL particles. The gene discussed is HMGCR; the disease is Hypercholesterolemia.