TARS1 (threonyl-tRNA synthetase 1) is a cytoplasmic enzyme that catalyzes the aminoacylation of threonine to tRNA(Thr) through a two-step ATP-dependent reaction, forming Thr-AMP before transfer to the tRNA acceptor end 12. Beyond its canonical translational role, TARS1 functions in gene expression regulation, cell signaling, angiogenesis, and inflammatory responses through non-canonical mechanisms 3. Notably, TARS1 activates the oncogenic transcription factor STAT3 independent of its catalytic activity by serving as a scaffold protein that promotes JAK-STAT3 proximity and phosphorylation, with elevated TARS1 expression correlating with poor survival in lung cancer 4. Loss-of-function TARS1 variants cause recessive phenotypes including brittle hair and multi-tissue involvement affecting the nervous system, lungs, and skin, as demonstrated in compound heterozygous mouse models 56. TARS1 has been identified as a candidate salivary biomarker in temporomandibular joint osteoarthritis 7. These findings establish TARS1 as a multifunctional protein with both essential translational roles and emergent non-canonical functions in disease pathogenesis.