GATC (glutamyl-tRNA amidotransferase subunit C) is a mitochondrial enzyme that catalyzes the transamidation of misacylated glutamyl-tRNA into correctly charged glutaminyl-tRNA. This reaction occurs in the presence of glutamine and ATP through an activated gamma-phospho-glutamyl-tRNA intermediate, ensuring accurate protein synthesis in mitochondria. The enzyme is part of the glutamyl-tRNA amidotransferase complex and functions as a quality-control step in mitochondrial translation. Loss-of-function variants in GATC cause combined oxidative phosphorylation deficiency 42 (COXPD42), a mitochondrial disorder characterized by impaired energy metabolism. This disease reflects the critical role of accurate aminoacyl-tRNA biosynthesis in sustaining the high protein synthetic demands of oxidative phosphorylation. Biallelic GATC mutations lead to defective mitochondrial protein synthesis and respiratory chain dysfunction, resulting in multisystem manifestations affecting skeletal development and other tissues dependent on mitochondrial ATP production. No current disease-specific therapeutics targeting GATC mutations have been approved, making gene therapy approaches or direct enzyme replacement potential avenues for future intervention. Understanding GATC function has implications for broader mitochondrial medicine, as transamidation pathways represent fundamental checkpoints in translational fidelity.