DHRS4L2 (dehydrogenase/reductase 4 like 2) is a paralogue of DHRS4 that arose through gene duplication and represents the most recent member of the human DHRS4 gene cluster on chromosome 14 1. The protein functions as a probable oxidoreductase with NADPH-dependent carbonyl reductase activity, localizing to mitochondria and peroxisomes where it participates in retinal metabolic processes. DHRS4L2 exhibits complex transcriptional regulation involving alternative splicing variants and antisense RNA-mediated silencing 2. The gene's expression is controlled by CpG island methylation in its promoter region, making it the only member of the DHRS4 cluster with hypermethylated CpG islands 3. A natural antisense transcript (AS1DHRS4) regulates DHRS4L2 expression through epigenetic mechanisms including histone modifications and DNA methylation 4. Clinically, DHRS4L2 variants have been associated with Alzheimer's disease age of onset, with certain genotypes accelerating disease onset by approximately 8 years 5. The gene has also been identified as a potential therapeutic target in prostate cancer, where it may be involved in lipid metabolism reprogramming 6. Additionally, DHRS4L2 methylation patterns are altered in response to persistent organic pollutant exposure 7.