GFM1 encodes a mitochondrial GTPase essential for translational elongation in mitochondria 1. It catalyzes GTP-dependent ribosomal translocation, enabling coordinated movement of tRNAs, mRNA, and ribosomal conformational changes during the pre- to post-translocational transition 2. Pathogenic GFM1 mutations impair mitochondrial protein synthesis, reducing expression of oxidative phosphorylation (OXPHOS) complexes and triggering compensatory mitophagy and unfolded protein response (UPRmt) activation 3. Clinically, GFM1 mutations cause combined oxidative phosphorylation deficiency characterized by neonatal-onset neurological disease—predominantly axial hypotonia, dystonia, and seizures with basal ganglia and brainstem involvement—frequently complicated by hepatic dysfunction 2. Disease severity correlates with mutation-induced protein instability affecting inter-domain interactions 3. Therapeutically, activating the mitochondrial unfolded protein response via tetracycline, polydatin, or nicotinamide partially restores mitochondrial protein synthesis and cellular bioenergetics in patient-derived cells, offering a promising disease-modifying strategy 1, 4. Additionally, GFM1 has emerged as a lactate-related hub gene in esophageal squamous cell carcinoma, though its specific oncogenic role requires clarification 5.