NDST4 (N-deacetylase and N-sulfotransferase 4) is a bifunctional enzyme catalyzing both N-deacetylation and N-sulfation of glucosamine residues in heparan sulfate biosynthesis 1. The enzyme exhibits weak deacetylase activity but high sulfotransferase activity, converting GlcNAc-containing disaccharide repeats to N-sulfated heparosan, a critical substrate for downstream heparin modifications 1. NDST4 expression is restricted to specific tissues including the brain, lung, gastrointestinal tract, pancreas, and ovary 1. In disease contexts, NDST4 functions as a putative tumor suppressor. Genetic loss of NDST4 at chromosome 4 is significantly associated with advanced colorectal cancer stages and poorer overall survival 2. Ndst4-deficient mice exhibit altered colonic epithelial homeostasis, including increased goblet cell numbers, decreased colonocyte populations, and elevated apoptosis 3, suggesting NDST4 directs biosynthesis of specific heparan sulfate proteoglycans essential for epithelial maintenance 3. Beyond cancer, NDST4 genetic variants associate with circulating resistin levels, an inflammatory marker linked to metabolic and cardiovascular disease 4. Additionally, NDST4 variants show associations with alcohol consumption phenotypes and complex neuropsychiatric disorders including bipolar disorder 56.