In addition to acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1), an enzyme in the endoplasmic reticulum of cells found ubiquitously throughout the body, data recently obtained in at least three mammalian species, including nonhuman primates, mice and humans, demonstrate the presence of an additional ACAT (EC 2.1.3.26), termed ACAT2, which is localized to the endoplasmic reticulum of liver and intestine. Data suggest that ACAT2 may be the enzyme responsible for cholesteryl ester secretion into apolipoprotein B-containing lipoproteins. We have hypothesized that oversecretion of cholesteryl esters produced by the action of hepatic ACAT2 could account for the increased atherogenicity associated with cholesteryl ester-enriched LDL in nonhuman primates. In such cases, ACAT2 is an appealing target for therapy to reduce coronary heart disease.