NDST3 (N-deacetylase and N-sulfotransferase 3) is a bifunctional enzyme that traditionally functions in heparan sulfate biosynthesis by catalyzing both N-deacetylation and N-sulfation of glucosamine residues [UniProt]. However, recent research has revealed an expanded role for NDST3 as a novel histone deacetylase (HDAC) family member that specifically deacetylates α-tubulin 1. This tubulin deacetylation activity critically regulates lysosomal function by suppressing V-ATPase assembly and reducing lysosomal acidification 1. NDST3 demonstrates significant clinical relevance across multiple neurological and psychiatric disorders. The enzyme is downregulated in tissues from ALS/FTD patients with C9orf72 mutations, and its deficiency exacerbates proteotoxicity from pathogenic poly-dipeptides 1. Genetic variants in NDST3, particularly rs11098403, show association with schizophrenia risk in Han Chinese populations 2. Additionally, NDST3 variants influence salt sensitivity and blood pressure regulation through modulation of heparan sulfate composition 3. Emerging evidence suggests therapeutic potential, with NDST3-mediated epigenetic reprogramming demonstrating ability to reverse neurodegeneration and restore motor function in Parkinson's disease models 4. These findings position NDST3 as a promising therapeutic target for neurodegenerative diseases through its dual roles in microtubule acetylation and lysosomal function 5.