ASS1 (argininosuccinate synthase 1) is a key urea cycle enzyme catalyzing the conversion of citrulline, aspartate, and ATP into argininosuccinate, thereby detoxifying ammonia produced during protein catabolism and enabling arginine biosynthesis in tissues 1. Beyond classical urea cycle function, ASS1 plays critical roles in immune regulation and cellular metabolism. In macrophages, ASS1-mediated citrulline depletion is required for proinflammatory activation through JAK2-STAT1 signaling, with citrulline acting as an innate immune-signaling metabolite 2. ASS1 expression increases following inflammatory stimuli, supporting an aspartate-argininosuccinate metabolic shunt that influences interferon responses 3. In cancer biology, ASS1 downregulation contributes to poor prognosis by diverting aspartate toward pyrimidine synthesis; conversely, ASS1 supports p53-mediated DNA damage responses through nuclear succination of chr9 remodeling complexes and cytosolic nucleotide restriction 4. ASS1 also confers ferroptosis resistance in lung cancer through glutamine reductive carboxylation and de novo fatty acid synthesis 5. Loss-of-function mutations in ASS1 cause citrullinemia type 1, an autosomal recessive urea cycle disorder with variable phenotypes ranging from neonatal hyperammonemia to asymptomatic presentations; residual ASS1 activity reliably predicts disease severity 16. Recent evidence suggests ASS1 inhibition may benefit inflammatory conditions including ulcerative colitis 7.