Lecithin retinol acyltransferase (LRAT) (LRAT)

Lecithin retinol acyltransferase (LRAT) is a membrane-bound enzyme primarily expressed in the retinal pigment epithelium (RPE) and the liver, where it plays a fundamental role in vitamin A metabolism (UniProt: Q9UL14). In the eye, LRAT is a key component of the visual retinoid cycle, responsible for the esterification of all-trans-retinol into all-trans-retinyl esters (PubMed: 10611246). These esters are the essential substrates for RPE65, the isomerase that produces 11-cis-retinal, the chromophore required for phototransduction in both rod and cone photoreceptors (PubMed: 15131254). Deficiencies in LRAT lead to a lack of 11-cis-retinal, resulting in severe inherited retinal dystrophies such as Leber congenital amaurosis type 14 (LCA14) and retinitis pigmentosa type 21 (RP21) (PubMed: 14508707). Therapeutic interventions under investigation include gene replacement therapy using adeno-associated virus (AAV) vectors to restore LRAT expression and pharmacological bypass using synthetic retinoids like 9-cis-retinyl acetate (QLT091001) (PubMed: 24827018). Monitoring treatment efficacy typically involves functional visual assessments such as electroretinography and visual field testing (PubMed: 26055813).

Other names

Phosphatidylcholine--retinol O-acyltransferaseLecithin-retinol acyltransferaseLCA14RP21

Substrate replacement therapy to bypass enzymatic blocks and gene replacement therapy to restore endogenous enzyme activity.