DHRS3 (dehydrogenase/reductase 3) is a microsomal, NADPH-dependent enzyme that catalyzes the reduction of all-trans-retinal to all-trans-retinol 1. As a member of the SDR16C family, DHRS3 plays a critical role in maintaining appropriate retinoic acid levels by forming a codependent complex with RDH10 that facilitates negative feedback regulation 2. Beyond retinoid metabolism, DHRS3 metabolizes endogenous compounds including androstenedione and estrone, and biotransforms xenobiotics 1. DHRS3 expression is regulated by p53 and p63 tumor suppressors, suggesting roles in tumor suppression and developmental processes 3. DHRS3 is expressed in liver, testis, and small intestine 1, and localizes to lipid droplets where it regulates melanoma cell state transitions through retinoic acid signaling 4. Biallelic hypomorphic variants in DHRS3 cause a novel developmental syndrome characterized by elevated retinoic acid, coronal craniosynostosis, facial dysmorphism, congenital heart disease, and scoliosis 5. DHRS3 upregulation during osteogenic differentiation is suppressed by miR-223, regulating bone formation 6. Additionally, DHRS3 demonstrates potential in gastric cancer pathogenesis and prognosis through feedback regulation with IRF1 and serves as a biomarker in papillary thyroid cancer 7, 8.