Sterol O-acyltransferase (often referred to as Acyl-coenzyme A: cholesterol acyltransferase) (ACAT)

Acyl-coenzyme A: cholesterol acyltransferase (ACAT) is an intracellular, membrane-bound enzyme located primarily in the endoplasmic reticulum. It is responsible for converting cholesterol and fatty acyl-CoA into cholesteryl esters, facilitating cholesterol storage within lipid droplets and contributing to lipoprotein synthesis. There are two main isoforms, ACAT1 (ubiquitous except intestine) and ACAT2 (mainly liver and intestine), encoded by separate genes and involved in tissue-specific cholesterol metabolism. ACAT activity safeguards cells from the toxicity of excess free cholesterol, but is also implicated in pathological lipid accumulation, such as foam cell formation in atherosclerosis and in Alzheimer’s disease models. As a result, ACAT is a key target for drug development—with multiple inhibitors explored to reduce cardiovascular risk. Notable therapeutic challenges include toxicity (especially adrenal), and the complexity of tissue-specific cholesterol metabolism

Other names

Sterol O-acyltransferaseAcyl-CoA cholesterol acyltransferaseAcyl-CoA cholesterin acyltransferaseSOATACAT1 (isoform 1)ACAT2 (isoform 2)

Inhibition of cholesterol esterification: drugs suppress ACAT activity, reducing the formation of cholesteryl esters from cholesterol and fatty acyl-CoA Modulation of foam cell formation and cholesterol uptake/storage Effects on lipoprotein secretion and metabolism