ARSA encodes arylsulfatase A, a lysosomal hydrolase that catalyzes the breakdown of cerebroside sulfate, a crucial step in lipid metabolism 1. The enzyme localizes to lysosomes and functions in sulfuric ester hydrolysis, with activity detectable in peripheral blood mononuclear cells and cerebrospinal fluid 2. ARSA deficiency causes metachromatic leukodystrophy (MLD), a neurodegenerative lysosomal storage disorder characterized by progressive demyelination and motor/cognitive impairment 1. MLD presents in three age-dependent subtypes (late-infantile, early-juvenile, and adult-onset), with disease severity correlating to ARSA mutation functional effects; approximately 36% of variants of unknown significance may be pathogenic 3. Recent evidence suggests rare ARSA variants associate with Parkinson's disease, identified among putative disease-causing genes in genetic PD cohorts, though findings require further validation 45. Clinically, atidarsagene autotemcel (arsa-cel), a lentiviral hematopoietic stem cell gene therapy delivering functional ARSA cDNA, demonstrates substantial therapeutic benefit in presymptomatic and early-symptomatic MLD patients, preserving motor and cognitive function with median 6-year follow-up showing 100% survival without severe motor impairment in treated presymptomatic late-infantile MLD versus 0% in untreated controls 62.