Functional testing of the variants confirmed the pathogenicity in a zebrafish model.<h4>Conclusion</h4>We define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity. The gene discussed is TARS2; the disease is inborn mitochondrial metabolism disorder.