1 Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire; 2 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Submitted 12 November 2008 ; accepted in final form 12 January 2009 ABSTRACT The enzymes acyl-coenzyme A (CoA):cholesterol acyltransferases (ACATs) are membrane-bound proteins that utilize long-chain fatty acyl-CoA and cholesterol as substrates to form cholesteryl esters. In mammals, two isoenzymes, ACAT1 and ACAT2, encoded by two different genes, exist. ACATs play important roles in cellular cholesterol homeostasis in various tissues. This chapter summarizes the current knowledge on ACAT-related research in two areas: 1 ) ACAT genes and proteins and 2 ) ACAT enzymes as drug targets for atherosclerosis and for Alzheimer's disease. acyl-coenzyme A:cholesterol acyltransferase inhibitors; atherosclerosis; Alzheimer's disease Address for reprint requests and other correspondence: T. Y. Chang, Dept. of Biochemistry, Dartmouth Medical School, 1 Rope Ferry Rd., Hanover, NH 03755-1404 (e-mail: Ta.Yuan.Chang{at}Dartmouth.edu )