SRD5A2 encodes steroid 5-alpha-reductase type 2, a critical enzyme that converts testosterone into 5-alpha-dihydrotestosterone (DHT), a more potent androgen 1. This conversion is essential for male sexual differentiation and urethral development during fetal growth 2. The enzyme is particularly important in ventral urethral tissues where it shapes male genital anatomy 2. Clinically, SRD5A2 loss-of-function mutations cause pseudovaginal perineoscrotal hypospadias, a congenital condition where the urethral opening is abnormally positioned 2. Genetic polymorphisms in SRD5A2, particularly the V89L variant, increase hypospadias risk significantly (OR=2.46 in dominant model) 2. The C allele at this locus functions as a genetic risk factor for disease occurrence 2. Regarding cancer associations, multiple large meta-analyses found no significant association between SRD5A2 polymorphisms and prostate cancer risk 341, despite initial smaller studies suggesting potential links. Similarly, V89L and TA repeat polymorphisms showed no association with breast cancer susceptibility 5. However, SRD5A2 variants influence metabolite profiles and may contribute to adverse drug effects, highlighting broader metabolic roles 6.