Lecithin retinol acyltransferase (LRAT)

Lecithin retinol acyltransferase (LRAT) is a microsomal enzyme key to vitamin A metabolism, encoded by the LRAT gene in humans[1][2]. LRAT catalyzes the esterification of all-trans-retinol (vitamin A alcohol) to all-trans-retinyl esters, a necessary step in both storing vitamin A and regenerating the visual chromophore in the retina. It transfers an acyl group from phosphatidylcholine to retinol, producing fatty acid retinyl esters such as palmitoyl and stearoyl retinyl esters. LRAT is abundantly expressed in the liver—where it supports dietary vitamin A storage—and in the retinal pigment epithelium (RPE), where it is indispensable for maintaining vision via the retinoid cycle. Genetic deficiency of LRAT causes a severe, early-onset form of retinal dystrophy (Leber congenital amaurosis, LCA14), which leads to retinal degeneration and vision loss[2][3]. LRAT has also been identified as being overexpressed in certain cancers, with clinical significance in colorectal cancer prognosis[1]. Small molecule drugs and gene therapies are under investigation to compensate for LRAT mutations or to modulate its activity (for instance, chromophore replacement therapy for LCA, or LRAT inhibitors for cosmetic use to boost skin retinol)[2][4]. The enzyme is a validated therapeutic target for inherited retinal diseases and an experimental target in dermatology and oncology[2][5].

Other names

Lecithin:retinol acyltransferaseLCA14phosphatidylcholine--retinol O-acyltransferaseretinyl ester synthase

Chromophore replacement therapy (such as 9-cis-retinyl acetate): provides exogenous retinoid to substitute for lack of native chromophore in LRAT deficiency[2][3] Inhibition of LRAT: blocks esterification of retinol, increasing free retinol availability in tissues such as skin[4]