NDST1 encodes a bifunctional enzyme that catalyzes both N-deacetylation and N-sulfation of N-acetyl-glucosamine residues during heparan sulfate (HS) biosynthesis 1. This enzymatic activity is essential for determining the overall structure and sulfation degree of HS polysaccharide chains, which influences downstream enzymatic modifications 1. NDST1 functions within a complex of HS biosynthetic enzymes, forming what has been termed a "GAGosome," where it interacts with other enzymes like EXT2 to regulate HS biosynthesis 2. The enzyme is particularly critical for fibroblast growth factor (FGF) signaling, as NDST1 deficiency reduces FGF protein binding to their receptors and disrupts downstream phospho-Erk signaling 3. Loss-of-function mutations in NDST1 cause autosomal recessive intellectual disability, with affected individuals showing complete loss of N-sulfotransferase activity while retaining N-deacetylase function 14. NDST1 shows the highest and most homogeneous expression in human cerebral structures compared to other NDST family members 1. In mice, Ndst1 knockout results in severe developmental defects including cerebral hypoplasia, lack of olfactory bulbs, eye defects, and craniofacial abnormalities, with homozygous null mutations being perinatally lethal 54.