Insulin-induced gene (InSig) localizes in the endoplasmic recticulum(ER) and is highly expressed in the liver and fibroblast cell lines. InSig1 and InSig2 play important roles in the regulation of cholesterol biosynthesis. Sterol induces InSig1 binding to the sterol-sensing domain of SREBP cleavage-activating protein (SCAP). Both InSig1 and Insig2 prevent the export of SCAP from the ER and thus, inhibit cholesterol synthesis by preventing the proteolytic cleavage of SREBPs by the Golgi enzymes.
