DDAH2 encodes a putative hydrolase that, despite its name, does not hydrolyze asymmetric dimethylarginine (ADMA), distinguishing it from DDAH1 which actively metabolizes ADMA 1. The protein appears to function primarily as a regulator of vascular and metabolic processes through ADMA-independent mechanisms. DDAH2 enhances endothelial function by inducing VEGF expression via SP1 phosphorylation and promotes pancreatic insulin secretion through SP1-mediated transcriptional regulation. Genetic polymorphisms in DDAH2 show significant associations with cardiovascular and metabolic diseases. The rs2272592 polymorphism is strongly associated with type 2 diabetes risk in Korean populations 2, while rs805305 variants correlate with coronary artery disease susceptibility 3. DDAH2 polymorphisms also influence ADMA levels in preeclampsia patients 4 and affect erythropoietin resistance in hemodialysis patients 5. Additionally, DDAH2 plays a role in innate immunity by relocating to mitochondria during viral infections to promote mitochondrial fission and inhibit antiviral responses. Expression analysis reveals DDAH2 predominates in highly vascularized tissues and shows altered co-expression patterns in psychiatric disorders 6, suggesting broader roles in neuropsychiatric conditions beyond its established vascular functions.