RDH16 (retinol dehydrogenase 16) functions as an NAD-preferring oxidoreductase that catalyzes the oxidation of retinol isomers (all-trans, 9-cis, 11-cis, and 13-cis-retinol) to their corresponding aldehydes, with higher activity toward CRBP-bound retinol compared to free retinol 1. The enzyme also exhibits 3-alpha-hydroxysteroid dehydrogenase activity, oxidizing androstanediol and androsterone to dihydrotestosterone and androstanedione 1. RDH16 plays a critical role in all-trans-retinoic acid (atRA) biosynthesis, which is regulated by energy status through insulin and FoxO1 signaling - insulin suppresses RDH16 expression via PI3K/Akt pathway inhibition of FoxO1, thereby reducing atRA production 1. In cancer contexts, RDH16 demonstrates complex roles: it acts as a tumor suppressor in hepatocellular carcinoma where its expression is typically silenced by hypermethylation, and demethylation by 5-azacytidine paradoxically promotes HCC metastasis through increased RDH16 expression 2. Additionally, RDH16 expression is epigenetically repressed by NSPc1 in glioma stem cells, contributing to cancer stem cell maintenance by limiting atRA synthesis 3. The gene serves as a prognostic biomarker in multiple cancers and shows associations with COVID-19 hospitalization risk 45.