NANS (N-acetylneuraminate synthase) is a key metabolic enzyme that catalyzes the synthesis of sialic acids, essential components of cellular glycoproteins and glycolipids. Specifically, NANS catalyzes the condensation of phosphoenolpyruvate (PEP) with N-acetylmannosamine 6-phosphate to produce N-acetylneuraminate-9-phosphate (Neu5Ac-9-P), the precursor for N-acetylneuraminic acid (Neu5Ac) 1. The enzyme also catalyzes production of deaminoneuraminic acid (KDN) 1. Beyond sialic acid biosynthesis, NANS functions as a ferroptosis regulator in cancer progression. In colorectal cancer, NANS suppresses NF-κB signaling to promote ferroptosis, with downregulation correlating with poor prognosis 2. Similarly, in prostate cancer, NANS serves as a prognostic biomarker; targeting NANS reverses immunosuppression through the sialoglycan-Siglec axis, inhibiting tumor growth 3. In hepatocellular carcinoma, NANS operates downstream of hexosamine pathway activation; NANS knockout reduces tumor growth and extends survival 4. Clinically, NANS mutations cause congenital disorder of glycosylation (CDG)-NANS, characterized by intellectual developmental disorder, skeletal dysplasia, and neurologic impairment 5. Preliminary sialic acid supplementation studies suggest potential therapeutic benefits, particularly with prenatal treatment 6.