{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARSG encodes a lysosomal sulfatase that plays a critical role in the hydrolytic removal of sulfate groups from substrates such as glycosaminoglycans. Biochemical and cellular analyses have demonstrated that ARSG undergoes glycosylation and proteolytic processing, with a key cysteine residue being post‐translationally modified to formylglycine – a modification essential for its catalytic activity – and is subsequently targeted from the endoplasmic reticulum to lysosomes (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " ARSG shows substrate specificity for 3‑O‑sulfated glucosamine residues in heparan sulfate, thereby contributing to the sequential lysosomal catabolism of this glycosaminoglycan (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Notably, genetic variants in ARSG have been implicated in a variety of clinical conditions. Several studies have linked ARSG mutations with atypical forms of Usher syndrome characterized by late-onset retinal degeneration and sensorineural hearing loss"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ", while deficiency of ARSG in mouse models leads to a lysosomal storage disorder with cerebellar degeneration and ataxia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, genome-wide association studies have identified ARSG variants as potential risk factors for conditions such as hypertension"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and task-specific dystonias including musician’s dystonia and writer’s cramp."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings underscore the importance of ARSG in lysosomal degradation pathways and cellular homeostasis, with its dysfunction contributing to a diverse spectrum of pathophysiological conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paola Ferrante, Silvia Messali, Germana Meroni, et al. 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