GLA encodes α-galactosidase A, a lysosomal hydrolase that catalyzes the degradation of glycosphingolipids, particularly glycosylceramide and globotriaosylceramide (Gb3) 1. The enzyme functions as a homodimer in the lysosomal lumen, where it participates in glycoside catabolism and oligosaccharide metabolism 2. Mutations in the GLA gene cause Fabry disease, an X-linked lysosomal storage disorder characterized by systemic pathology 1. Loss of α-Gal A activity results in pathological Gb3 accumulation in multiple organs 3. Affected males (hemizygous) typically manifest classical disease, while heterozygous females exhibit variable phenotypes depending on X-chromosome X patterns and allele-specific DNA methylation at the GLA promoter 45. Fabry disease presents with multi-organ dysfunction including ischemic stroke, peripheral neuropathy, cardiac dysfunction, and chrX kidney disease 1. Pathogenic GLA variants consistently associate with disease features, while variants of uncertain significance may acquire Fabry phenotypes only in patients with elevated cardiovascular risk burden 5. Clinical interventions include enzyme replacement therapy, chaperone therapy (migalastat), which improves enzyme activity particularly in missense mutations with minor protein conformational changes 2, and emerging AAV9-mediated gene therapy, which demonstrates superior biodistribution and efficacy compared to AAV8 vectors 3.