Phosphatidylcholine-sterol acyltransferase (LCAT)

Phosphatidylcholine-sterol acyltransferase, commonly known as Lecithin-cholesterol acyltransferase (LCAT), is a plasma enzyme primarily synthesized in the liver that plays a critical role in cholesterol homeostasis [2, 7]. It catalyzes the transfer of a fatty acyl group from phosphatidylcholine to free cholesterol, producing cholesteryl esters and lysophosphatidylcholine [3, 8]. This reaction is essential for the maturation of nascent, discoidal high-density lipoproteins (HDL) into mature, spherical particles, which is a rate-limiting step in the reverse cholesterol transport pathway [7, 11]. Genetic deficiencies in LCAT lead to rare disorders such as familial LCAT deficiency (FLD) and fish-eye disease (FED), characterized by low HDL levels and systemic complications like corneal opacities and progressive renal failure [2, 9]. As a therapeutic target, LCAT is being explored through enzyme replacement therapies (e.g., ACP-501, MEDI6012) and small molecule activators (e.g., DS-8190a) to treat genetic deficiencies and potentially mitigate cardiovascular risks associated with atherosclerosis [1, 21, 24].

Other names

Lecithin-cholesterol acyltransferasePhospholipid-cholesterol acyltransferaseLysolecithin acyltransferase

Enzyme replacement therapy (recombinant human LCAT) or small molecule activation to restore or enhance the esterification of free cholesterol on HDL particles, promoting reverse cholesterol transport [1, 21, 24].