GNS encodes N-acetylglucosamine-6-sulfatase, a lysosomal enzyme that hydrolyzes 6-sulfate groups from N-acetyl-D-glucosaminide units in heparan sulfate and keratan sulfate 1. This enzyme functions as a sulfuric ester hydrolase critical for glycosaminoglycan catabolism, participating in the sequential degradation of heparan sulfate within lysosomes 2. GNS mutations cause mucopolysaccharidosis type IIID (MPS IIID, Sanfilippo syndrome subtype D), a lysosomal storage disorder characterized by progressive heparan sulfate accumulation in lysosomes and extracellular compartments 1. This leads to secondary storage of glycosphingolipids, oxidative stress, and neuroinflammation, predominantly affecting the central nervous system with progressive cognitive decline and severe hyperactivity 1. A case report identified a novel homozygous GNS truncating mutation in a family presenting with the unusual combination of mucopolysaccharidosis and retinal dystrophy, expanding the clinical spectrum of GNS-associated disease 3. Additionally, GNS mutations are recognized among carbohydrate-linked lysosomal storage diseases presenting cardiac complications 4. Currently, no established cure exists; however, enzyme replacement therapy and gene therapy show promise in clinical trials for managing MPS III 2.