GTPBP3 is a mitochondrial GTPase that catalyzes 5-taurinomethyluridine (τm5U) modification at the wobble position (U34) of mitochondrial tRNAs 1. As the GTPase component of the GTPBP3-MTO1 complex, GTPBP3 cooperatively functions with MTO1 to enable this critical tRNA modification 1. The τm5U modification is essential for accurate codon-anticodon base pairing during mitochondrial translation, particularly at lysine (AAG) and leucine (UUG) codons 2. GTPBP3 is ubiquitously expressed in metabolically active tissues including heart, liver, and brain 3. Loss-of-function mutations in GTPBP3 cause Combined Oxidative Phosphorylation Deficiency 23 (COXPD23), a rare mitochondrial disorder characterized by hyperlactatemia, hypertrophic cardiomyopathy, seizures, developmental delay, and neurological symptoms 45. τm5U hypomodification due to GTPBP3 deficiency impairs mitochondrial translation, reducing expression of respiratory chain enzymes and compromising oxidative phosphorylation 2. Severe phenotypes correlate with homozygous variants and loss-of-function mutations concentrated in the TrmE-type G domain 4. The disease shows variable severity, with early childhood mortality in severe cases and developmental delay predominating in milder presentations 46.