CPS1 (carbamoyl-phosphate synthase 1) is the rate-limiting mitochondrial enzyme of the urea cycle that catalyzes ammonia detoxification by converting ammonia and bicarbonate to carbamoyl phosphate 1. In normal hepatocytes, CPS1 plays a critical role in removing excess ammonia from cells, preventing ammonia-induced toxicity 1. Beyond canonical ammonia metabolism, CPS1 maintains pyrimidine biosynthesis through an unconventional nitrogen pathway, sustaining DNA synthesis and cell cycle progression 2. Mutations in CPS1 cause severe carbamoyl-phosphate synthetase 1 deficiency, a rare genetic disorder with approximately 50% early infant mortality, characterized by hyperammonemia and neurological complications 3. In cancer biology, CPS1 exhibits context-dependent roles: it is downregulated in hepatocellular carcinoma (HCC) where low expression correlates with poor prognosis, yet functions as a metabolic switch balancing cell proliferation and metastasis by regulating aspartate levels 4. The tumor suppressor p53 represses CPS1 transcription to suppress ureagenesis and accumulate ammonia, which inhibits polyamine biosynthesis and cell proliferation 5. Recent advances include successful in vivo base-editing therapy correcting CPS1 mutations in a neonatal patient, demonstrating therapeutic potential for this severe genetic disease 3.