Acyl-coenzyme A: cholesterol O-acyltransferase 2 (ACAT2)

Acyl-coenzyme A: cholesterol O-acyltransferase 2 (ACAT2) is a membrane-bound enzyme located in the endoplasmic reticulum that catalyzes the intracellular formation of cholesteryl esters from cholesterol and long-chain fatty acyl-CoA. ACAT2, together with ACAT1 (a closely related isoenzyme), regulates cholesterol storage and transport in mammalian cells. While ACAT1 is ubiquitous, ACAT2 expression is tissue-restricted, mainly found in the liver and intestine, where it plays a critical role in lipoprotein assembly and dietary cholesterol absorption. In disease states such as atherosclerosis, ACAT2 is upregulated in macrophages within atherosclerotic plaques, contributing to foam cell formation and lesion progression. Selective inhibition of ACAT2 has been investigated as a therapy for hypercholesterolemia and cardiovascular disease, and ACAT2 is considered a promising drug target in this context. The structure of human ACAT2 features a catalytic site for cholesterol esterification and regulatory sites, providing insights for the development of isoform-selective inhibitors.

Other names

Acyl-CoA: cholesterol acyltransferase 2Sterol O-acyltransferase 2SOAT2

Inhibitors block the esterification of cholesterol by ACAT2, reducing the formation of cholesteryl esters that contribute to lipoprotein assembly and foam cell formation, thereby attenuating hypercholesterolemia and atherosclerosis.