ARSB encodes arylsulfatase B, a lysosomal enzyme that catalyzes the hydrolysis of 4-sulfate groups from N-acetylgalactosamine residues on glycosaminoglycans, particularly dermatan sulfate and chondroitin-4-sulfate 1. The enzyme contains a catalytically essential formylglycine residue that is posttranslationally modified to hydroxylformylglycine, enabling sulfate ester bond hydrolysis 2. Beyond degradative function, ARSB regulates cell adhesion, migration, and invasion in colonic epithelium, and modulates neurite outgrowth and neuronal plasticity through control of sulfated glycosaminoglycans 3. ARSB deficiency causes Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome), an autosomal recessive lysosomal storage disorder characterized by progressive multisystem involvement, skeletal dysplasia, cardiac valve disease, and variable neurological complications, with prevalence between 1 in 43,261 and 1 in 1,505,160 live births 1. Over 130 ARSB mutations have been reported, predominantly missense variants (85% of mutations), causing absent or severely reduced enzyme activity 4. ARSB is clinically significant as a candidate gene for newborn genome sequencing, recommended by 85% of rare disease experts for early detection of treatable MPS VI cases 5. Enzyme replacement therapy with galsulfase provides the primary treatment, improving endurance and mobility in affected individuals 1.