SLC25A2 encodes a mitochondrial transporter of cationic amino acids, primarily functioning as an ornithine/lysine/arginine antiporter. 1 The protein transports positively charged amino acids including ornithine, lysine, arginine, and the neutral amino acid citrulline, as well as histidine, homoarginine, and asymmetric dimethylarginine (ADMA), but not symmetric dimethylarginine. 12 SLC25A2 operates via both counter-exchange and unidirectional transport mechanisms. 2 A major physiological function is ADMA export from mitochondria, as SLC25A2 efficiently transports ADMA in both directions with kinetics nearly equivalent to canonical substrates. 2 The protein exhibits broad tissue expression, with highest levels in liver. 1 Clinically, SLC25A2 mutations are associated with the urea cycle disorder hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, though SLC25A2 provides partial functional redundancy with the primary defective transporter SLC25A15. 3 Recent evidence suggests SLC25A2 variants may predict neoadjuvant chemoradiotherapy response in rectal cancer patients. 4 Notably, SLC25A2 knockout mice show no fertility defects, indicating the gene is dispensable for male reproduction when individually ablated. 5