ACAT2

ACAT2 (sterol O-acyltransferase 2, SOAT2) is an endoplasmic reticulum membrane enzyme that catalyzes the esterification of cholesterol with long-chain fatty acyl-CoA, generating cholesteryl esters that support intracellular cholesterol storage and lipoprotein assembly^[1][2]. Mechanistically, ACAT2 maintains cholesterol homeostasis by channeling free cholesterol into cholesteryl ester pools that are subsequently incorporated into chylomicrons and apoB-containing lipoproteins in intestinal and hepatic tissues^[2][3]. Therefore, ACAT2 is closely linked to dietary cholesterol absorption, hepatic cholesterol esterification, and the production of atherogenic lipoproteins in metabolic disease models^[2][4]. In disease settings, genetic or tissue-specific suppression of ACAT2 reduces hepatic cholesteryl ester accumulation, hypercholesterolemia, and atherosclerotic burden, supporting its relevance in cardiovascular and lipid metabolism research^[4]. Compared with the related isoform ACAT1 (SOAT1), which is broadly expressed across tissues, ACAT2 shows predominant expression in hepatocytes and intestinal cells and exhibits a more specialized role in lipoprotein-associated cholesterol ester metabolism^[1][3]. For experimental applications, several ACAT2-selective inhibitors, including pyripyropene A derivatives, have been used to decrease cholesterol esterification and attenuate atherosclerotic phenotypes in mouse models, providing pharmacological tools for investigating cholesterol transport pathways and therapeutic target validation^[5].