MTRFR (mitochondrial translation release factor in rescue) is a critical component of mitochondrial ribosome quality control that responds to aberrant translation events. As a heterodimer with MTRES1, MTRFR ejects unfinished nascent chains and peptidyl-tRNA from stalled mitoribosomes, preventing accumulation of aberrant translation products 1. The protein functions as a peptidyl-tRNA hydrolase within the mitoribosomal large subunit, with recruitment of mitoribosome biogenesis factors suggesting roles beyond ribosome rescue 1. MTRFR is essential for resolving nonstop mRNA complexes that evade canonical termination mechanisms, thereby maintaining mitochondrial protein synthesis fidelity 2. Pathogenic variants in MTRFR are loss-of-function mutations that cause MTRFR deficiency, with homozygous truncating mutations proving embryonically lethal in mice 3. MTRFR dysfunction impairs mitochondrial protein synthesis quality control, particularly affecting the 13 oxidative phosphorylation complex subunits synthesized within mitochondria 1. Clinically, MTRFR mutations associate with combined oxidative phosphorylation deficiency 7 and spastic paraplegia 55 (autosomal recessive), manifesting as neurological dysfunction 4. Gene replacement strategies using AAV9 delivery successfully correct mitochondrial phenotypes in cellular models 3, suggesting therapeutic potential for this monogenic mitochondrial disorder.