Sterol O-acyltransferase 1; Sterol O-acyltransferase 2 (SOAT1; SOAT2)

Sterol O-acyltransferase 1 (SOAT1, also known as ACAT1) and Sterol O-acyltransferase 2 (SOAT2, also known as ACAT2) are membrane-bound enzymes located in the endoplasmic reticulum that catalyze the intracellular esterification of cholesterol with long-chain fatty acids to produce cholesterol esters, which are then stored in cytoplasmic lipid droplets. SOAT1 is broadly expressed across tissues except the intestine, while SOAT2 is primarily expressed in the liver and intestine and plays a significant role in the assembly of apoB-containing lipoproteins such as VLDL. Both enzymes are involved in cholesterol buffer systems and are implicated in the development and therapy of atherosclerosis, certain cancers, Alzheimer’s disease, and metabolic liver disorders. Pharmacological inhibitors of SOAT1 and SOAT2 have been investigated for cardiovascular, oncological, and endocrine diseases, but systemic effects and enzyme selectivity remain challenges for clinical application

Other names

SOAT1: Acyl-CoA:cholesterol acyltransferase 1, ACAT1SOAT2: Acyl-CoA:cholesterol acyltransferase 2, ACAT2

Inhibition of SOAT1/SOAT2 reduces cholesterol esterification, increases cellular free cholesterol, reduces foam cell formation, and may lower plasma cholesterol or inhibit cancer cell growth Inhibitors can prevent atherogenesis by decreasing atherogenic lipoprotein secretion and arterial lipid deposition Inhibition in cancer can disrupt metabolic adaptation and cholesterol homeostasis required for tumor growth