WARS2 encodes mitochondrial tryptophanyl-tRNA synthetase, which catalyzes the two-step aminoacylation of tryptophan to tRNA(Trp) for mitochondrial protein synthesis 1. Beyond its canonical role in translation, WARS2 functions as a determinant of angiogenesis, with reduced enzyme activity impairing endothelial cell angiogenesis and cardiac capillary density 2. The gene regulates brown adipose tissue (BAT) function and glucose metabolism; wild-type WARS2 increases mitochondrial respiration and glucose oxidation in BAT while reducing visceral adiposity 3. WARS2 variants associate with cardiovascular and metabolic disease susceptibility, appearing in genome-wide association studies as a regulator of visceral adiposity 4. Biallelic WARS2 mutations cause neurodevelopmental mitochondrial disorders with diverse phenotypes, ranging from neonatal-onset disease to dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia 56. Disease variants impair mitochondrial integrity and reduce full-length protein expression 5. A common hypomorphic missense variant (p.Trp13Gly) occurs in ~0.5% of Europeans and frequently appears in compound heterozygotes with truncating alleles 6. Beyond inherited disease, an intronic long noncoding RNA (WARS2-IT1) derived from the WARS2 locus influences colorectal cancer radioresistance through HIF-1α stabilization 7.