GAA (acid α-glucosidase) is a lysosomal enzyme essential for glycogen catabolism. It hydrolyzes α-1,4-linked glycosidic bonds with highest activity, and can also process α-1,6-linked glucans 1. The enzyme functions within lysosomes to degrade glycogen to glucose, supporting normal cellular metabolism 2. GAA deficiency causes Pompe disease, a neuromuscular lysosomal disorder characterized by pathological glycogen accumulation in muscle, heart, and other tissues 1. Two clinical phenotypes exist: infantile-onset Pompe disease (IOPD) with near-complete GAA deficiency presenting at birth and fatal by age 2 without treatment, and late-onset Pompe disease (LOPD) with partial GAA activity causing progressive muscle weakness and respiratory dysfunction 1. Among 1,079 Pompe disease patients, 2,075 GAA variants were identified, with clinical severity correlating to residual enzyme activity 3. Currently, enzyme replacement therapy (ERT) with recombinant human GAA represents standard care, with second-generation formulations (avalglucosidase alfa, cipaglucosidase alfa) offering improved cellular uptake and efficacy 24. Gene therapy using AAV9 vectors delivering GAA is emerging as potentially curative; early clinical trials in IOPD patients demonstrated cardiac and motor improvements 5, while LOPD trials show promise for discontinuing ERT post-therapy 1.