Insulin-induced gene 1 protein; Insulin-induced gene 2 protein (INSIG1; INSIG2)

Insulin-induced gene 1 protein (INSIG1) and Insulin-induced gene 2 protein (INSIG2) are closely related endoplasmic reticulum membrane proteins that regulate cholesterol homeostasis. They function by binding to the sterol-sensing domain of SCAP and HMG-CoA reductase, which sequesters these proteins in the ER, blocks SREBP activation, promotes HMG-CoA reductase degradation, and thereby tightly controls intracellular cholesterol synthesis. INSIGs additionally serve as oxysterol-binding proteins and mediate cell death in response to excess oxysterols, linking them to metabolic diseases and, through regulatory effects in cancer-related pathways, to tumor progression. Though not direct drug targets currently, their function is modulated by metabolic intermediates such as sterols, oxysterols, and vitamin D derivatives[1][2][3][4][5][6].

Other names

INSIGInsulin-induced gene 1 (for INSIG1)Insulin-induced gene 2 (for INSIG2)

Oxysterols bind to INSIG proteins causing retention of SCAP/SREBP complex in the ER, reducing cholesterol synthesis. INSIG-mediated regulation leads to HMG-CoA reductase degradation, inhibiting cholesterol production