GFM2 encodes a mitochondrial GTPase essential for terminating mitochondrial protein synthesis. As a GTP-dependent ribosome recycling factor, GFM2 mediates the disassembly of ribosomes from messenger RNA at the end of translation by dissolving intersubunit contacts and collaborating with MRRF 12. GTP hydrolysis occurs on the ribosomal large subunit following ribosome disassembly, and GFM2 is specifically uninvolved in translocation during elongation 1. GFM2 mutations cause Combined Oxidative Phosphorylation Deficiency 39, manifesting as Leigh syndrome with diverse neurological presentations. Patients with compound heterozygous or homozygous GFM2 variants present with global developmental delay, elevated cerebrospinal fluid lactate, cerebellar atrophy, and reduced OXPHOS subunit expression 34. Defective mitochondrial translation impairs energy production in affected tissues, creating a disconnect between increased mitochondrial respiratory proteins and decreased cellular respiration 5. Clinically, GFM2 variants account for a subset of early-onset mitochondrial diseases, with whole-exome sequencing identifying GFM2 mutations in patients presenting with microcephaly, arthrogryposis multiplex congenita, and insulin-dependent diabetes 6. GFM2 dysregulation is implicated in chr5 kidney disease pathogenesis through co-regulation with cytosolic ribosomal factors 5.