SRD5A3 encodes polyprenal reductase, a multifunctional oxidoreductase with dual roles in glycosylation and androgen metabolism. Primarily, SRD5A3 catalyzes the second step of dolichol biosynthesis by reducing polyprenol to dolichol in an NADP-dependent mechanism 1. Dolichols are essential lipid carriers for activated sugars and oligosaccharide precursors required for N-linked glycosylation 21. SRD5A3 also possesses steroid 5α-reductase activity, converting testosterone to 5α-dihydrotestosterone 34. Pathogenic variants in SRD5A3 cause SRD5A3-CDG (congenital disorder of glycosylation type I), an autosomal recessive disorder characterized by defective N-linked glycosylation 5. Affected patients exhibit multisystem involvement including psychomotor disability, cerebellar ataxia, visual impairment with nystagmus and optic neuropathy, skeletal anomalies, and variable hepatic dysfunction 67. N-glycoproteomic analysis of patient fibroblasts reveals widespread decreases in glycosylated proteins, particularly high-mannose and complex glycopeptides, alongside disrupted lysosomal and mitochondrial function 5. Cardiac complications including cardiomyopathy have been documented in SRD5A3-CDG patients 8. Beyond Mendelian disease, elevated SRD5A3 expression promotes hepatocellular carcinoma and triple-negative breast cancer growth and predicts poor survival 910.