Hypercholesterolemia in hypothyroidism is mainly due to a reduction in LDL receptor activity, accompanied by the weakened control effect of T3 on sterol regulatory element binding protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating the rate-limiting degrading enzyme 3-hydroxy-3-methylglutarylcoenzyme and reductase (HMG-CoA) activity. The gene discussed is SREBF2; the disease is Hypercholesterolemia.