GARS1 encodes glycyl-tRNA synthetase 1, a cytosolic enzyme that catalyzes the ATP-dependent ligation of glycine to its cognate tRNA (tRNAGly), a critical step in protein synthesis 123. Beyond translation, GARS1 produces diadenosine tetraphosphate (Ap4A), a pleiotropic signaling molecule involved in cellular regulation 4. GARS1 functions as a homodimer and localizes to the cytosol, mitochondrial matrix, and is secreted via extracellular vesicles 5. Pathogenic heterozygous GARS1 mutations cause autosomal dominant Charcot-Marie-Tooth disease type 2D and hereditary motor neuropathy through a gain-of-function mechanism involving tRNAGly sequestration 6. This sequestration depletes cellular tRNAGly pools, causing ribosome stalling at glycine codons and protein synthesis defects in peripheral neurons 6. GARS1 variants are among the most common causative genes in inherited peripheral neuropathies 7. Beyond neurological disease, GARS1 is upregulated across multiple cancer types and serves as a prognostic biomarker associated with poor survival 89. GARS1-containing extracellular vesicles promote M1 macrophage polarization and demonstrate anti-tumor activity 5. GARS1 expression correlates with immune infiltration and checkpoint markers, suggesting potential value in immunotherapy response prediction 9.