HGSNAT (heparan-alpha-glucosaminide N-acetyltransferase) is a lysosomal membrane acetyltransferase that catalyzes a unique transmembrane acetylation reaction essential for heparan sulfate degradation 1. The enzyme acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase 2. This involves transporting the acetyl group from cytosolic acetyl-CoA across the lysosomal membrane via a central pore within a dimeric enzyme structure, with catalysis mediated by a histidine-aspartic acid dyad 1. HGSNAT deficiency causes mucopolysaccharidosis type IIIC (Sanfilippo syndrome C), a severe autosomal recessive lysosomal storage disease characterized by heparan sulfate accumulation 2. Clinical presentation includes progressive neurological deterioration with onset typically around 4 years of age, featuring speech deterioration, mental decline, and hyperactivity, with relatively mild somatic symptoms 3. Additionally, biallelic HGSNAT variants can cause adult-onset nonsyndromic retinitis pigmentosa with pericentral retinal degeneration and reduced photoreceptor function, distinct from syndromic MPS IIIC 4. Current treatment options remain limited, though enzyme replacement therapy and gene therapy show promise 5. Cardiac complications have been documented in carbohydrate-linked lysosomal storage diseases including HGSNAT deficiency 6.