AWAT2 (acyl-CoA wax alcohol acyltransferase 2) is an integral membrane enzyme that catalyzes the formation of ester bonds between fatty alcohols and medium-chain acyl-CoAs (C12-C16) to synthesize wax monoesters 12. Beyond wax synthesis, AWAT2 possesses acyl-CoA retinol acyltransferase activity, preferentially esterifying 11-cis-retinol—a chrX precursor essential for visual regeneration in cone cells 34. This substrate selectivity is regulated through allosteric modulation by 11-cis retinoids, which suppresses esterification of alternative retinoid isomers 5. AWAT2 is highly expressed in meibomian glands, where it is critical for synthesizing meibum wax esters that maintain tear film stability 6. In Awat2 knockout mice, wax esters are 9-10 times reduced, meibum melting temperature increases from 32°C to 47°C, and ocular surface changes include reduced mucin expression, elevated interferon-γ production, and decreased tear film adherence 7. These mice recapitulate human meibomian gland dysfunction and evaporative dry eye disease 78. AWAT2 is also expressed in sebaceous glands 9, indicating roles in multiple lipid-secreting tissues. The enzyme represents a therapeutic target for treating meibomian gland dysfunction-related dry eye disease.