INSIG1

INSIG1, also known as Insulin Inducible Gene 1, is a gene that encodes a regulatory protein involved in cholesterol homeostasis within cells. It is primarily expressed in the liver, adrenal glands, and other tissues involved in lipid metabolism. The INSIG1 protein functions as an endoplasmic reticulum (ER) membrane protein, playing a vital role in the regulation of sterol regulatory element-binding proteins (SREBPs), which are key transcription factors controlling lipid synthesis.

The primary function of INSIG1 involves the retention of SREBPs in the ER, preventing their activation and subsequent movement to the Golgi apparatus where they promote the expression of genes involved in cholesterol and fatty acid synthesis. When cellular cholesterol levels are sufficient, INSIG1 binds to SCAP (SREBP cleavage-activating protein) and retains SREBPs in the ER, thus downregulating lipid production. Conversely, when cholesterol levels are low, INSIG1 releases its hold on SREBPs, allowing their activation and the subsequent synthesis of lipids.

INSIG1 expression is regulated by various signaling pathways, including those activated by sterols and other lipid-related molecules. It has garnered interest for its potential role in lipid disorders, cardiovascular diseases, and metabolic syndromes. Abnormalities or dysregulation of INSIG1 have been linked to altered cholesterol levels and associated pathologies.

Research continues to elucidate the precise mechanisms involving INSIG1 and its interactions within lipid metabolic pathways. Due to its central role in maintaining lipid balance, INSIG1 is considered a significant target for therapeutic strategies addressing metabolic and cardiovascular diseases.