Role of Lecithin: Cholesterol Acyltransferase in HDL Metabolism and Atherosclerosis

Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in lipoprotein metabolism that enables the maturation of high-density lipoprotein (HDL) particles. LCAT esterifies free cholesterol on the surface of HDL, forming cholesteryl esters which then partition into the lipoprotein core, resulting in the formation of mature spherical HDL particles. In this review, we explore the biochemistry of LCAT and its role in reverse cholesterol transport and lipid metabolism. We also describe fish eye disease and familial LCAT deficiency, two genetic disorders of LCAT. Given its role in facilitating the flux of cholesterol from peripheral tissue to the liver, we also examine the role of LCAT in the pathogenesis of atherosclerosis in animal models and human studies. Finally, we describe recent efforts in developing LCAT-based therapeutics.