NANS encodes N-acetylneuraminate synthase, a key enzyme catalyzing the condensation of phosphoenolpyruvate and N-acetylmannosamine 6-phosphate to synthesize N-acetylneuraminate-9-phosphate, a phosphorylated form of the sialic acid N-acetylneuraminic acid. The enzyme is required for brain and skeletal development. NANS functions beyond its canonical metabolic role in ferroptosis and immune regulation. In colorectal cancer, NANS suppresses metastasis by promoting ferroptosis susceptibility, though CDK1-mediated phosphorylation at serine 275 triggers its degradation and enables ferroptosis resistance 1. In prostate cancer, NANS protein serves as a prognostic biomarker for aggressive disease; targeting NANS reverses immunosuppression by restricting the sialoglycan–Siglec axis 2. Similarly, in c-Myc-driven hepatocellular carcinoma, NANS activation within the hexosamine-sialic acid pathway promotes tumorigenesis, and NANS knockout inhibits tumor growth and extends survival 3. Biallelic NANS variants cause NANS-congenital disorder of glycosylation (NANS-CDG), characterized by intellectual developmental disorder, skeletal dysplasia, neurologic impairment, and gastrointestinal dysfunction 4. Prenatal oral sialic acid supplementation may benefit neurodevelopmental outcomes, though evidence remains limited 5. These findings identify NANS inhibition as a potential therapeutic strategy for sialic acid-driven malignancies.