Insulin-induced gene 2 protein (INSIG2)

Insulin-induced gene 2 protein (INSIG2) is a polytopic membrane protein localized in the endoplasmic reticulum that participates in the feedback regulation of cholesterol biosynthesis by mediating the retention of the SREBP cleavage-activating protein (SCAP)/SREBP complex in the ER in response to sterol levels and by promoting the sterol-dependent degradation of HMG-CoA reductase[1][2][3]. By binding SCAP only in the presence of oxysterols (such as 25-hydroxycholesterol), INSIG2 prevents SREBPs from being processed in the Golgi, thereby blocking the transcription of genes required for lipid and cholesterol synthesis[1][2]. INSIG2 is structurally related to INSIG1, but it is regulated differently, being constitutively expressed and more reliant on the presence of sterols for activity[1]. It affects metabolic, cardiovascular, and cancer biology through its core role in sterol and fatty acid homeostasis[1][2][3][4].

Other names

INSIG2INSIG-2Insulin induced protein 2INSIG2 membrane protein

Statins: Block HMG-CoA reductase to reduce cholesterol synthesis, indirectly affected by INSIG2 activity. Fibrates/Thiazolidinediones: Modulate INSIG2 expression, resulting in inhibition of SREBP activation and downstream lipid synthesis.