Our present study showed that adipose-targeted T3 therapy retains the ability to reduce hypercholesterolemia in apoE−/− substantially mice with a defect in hepatic uptake of LDL-C, whereas LT3 treatment, which causes preferential accumulation of T3 in the liver, leads to only a relatively modest reduction in circulating cholesterol in apoE−/− mice, indicating that adipose tissue is another vital action site mediating the cholesterol-lowering activity of TH. Here, COG2 is linked to Hypercholesterolemia.