RDH16 (retinol dehydrogenase 16) is an NAD+-dependent oxidoreductase that catalyzes the oxidation of all-trans-retinol, 9-cis-retinol, 11-cis-retinol, and 13-cis-retinol to their corresponding aldehydes, with higher catalytic activity toward cellular retinol-binding protein-bound retinol than free retinol 1. The enzyme also oxidizes 3α-hydroxysteroids including androstanediol and androsterone to dihydrotestosterone and androstanedione, respectively, and can catalyze reversible reactions 2. RDH16 is localized to the endoplasmic reticulum membrane with its catalytic domain oriented toward the cytosol. RDH16 plays a critical role in retinoic acid biosynthesis, the rate-limiting step of which is regulated by energy status through insulin-FoxO1 signaling 3. Dysregulation of RDH16 associates with multiple pathological conditions: reduced expression occurs in endometrial cancers and hepatocellular carcinoma 45, while elevated expression correlates with improved survival outcomes in HCC patients 6. Recent evidence suggests RDH16 functions as a stemness suppressor in glioma, with epigenetic repression of RDH16 promoting cancer stem cell self-renewal 7. Additionally, a 2025 genome-wide association study identified RDH16 as a high-confidence risk gene for migraine without aura, implying involvement in vascular-metabolic pathways underlying migraine pathogenesis 8. At the mechanistic level, nerve growth factor upregulates RDH16 expression through farnesoid X receptor signaling, enhancing chemosensitivity to cisplatin and doxorubicin in HCC cells 6.