DHRS4 (dehydrogenase/reductase 4) is an NADPH-dependent oxidoreductase enzyme that catalyzes the reduction of carbonyl-containing compounds including ketosteroids, alpha-dicarbonyl compounds, aldehydes, and quinones 1. The enzyme participates in retinoid metabolism, 3-beta-hydroxysteroid metabolism, and detoxification of xenobiotic carbonyl compounds such as benzil 2. DHRS4 shares catalytic mechanisms with its paralog DHRS2, though substrate-binding sequences differ substantially, resulting in different substrate specificities between the two enzymes 3. DHRS4 is part of a gene cluster on chromosome 14.2 that includes paralogous genes DHRS4L1 and DHRS4L2, generated through mammalian gene duplication 4. The cluster is subject to complex transcriptional regulation involving alternative splicing, alternative transcription start sites, and epigenetic mechanisms; notably, the natural antisense transcript AS1DHRS4 regulates expression of all three cluster members through histone modifications and DNA methylation 5. Clinically, DHRS4 dysregulation has been implicated in neurodegeneration. In amyotrophic lateral sclerosis models, DHRS4 upregulation correlates with disease progression and may activate complement cascade-related immune responses contributing to neurodegeneration 6. Additionally, the DHRS4-AS1 antisense transcript suppresses osteosarcoma cell proliferation and may regulate inflammation in ulcerative colitis through competitive endogenous RNA mechanisms 78.