MTFR1 (mitochondrial fission regulator 1) is a conserved mitochondrial protein essential for regulating mitochondrial dynamics and aerobic respiration. MTFR1 localizes to mitochondria and promotes mitochondrial fission, with structural studies showing it binds to Miro proteins through a conserved hydrophobic pocket, positioning it as a universal mitochondrial adaptor 1. In normal physiology, MTFR1 is required for oxygen consumption and ATP synthesis; inhibition of MTFR1 severely impairs mitochondrial respiration in testicular cells 2. Under metabolic stress, MTFR1 undergoes phosphorylation at serine 119 by NEK1, shifting its function toward promoting mitochondrial fusion rather than fission, which enhances oxidative phosphorylation and supports cell survival during glucose deprivation in colon cancer 3. Additionally, MTFR1 regulates T cell mitochondrial function and metabolic programming; miR-142 silencing increases MTFR1 expression, leading to enhanced mitochondrial function and reduced T cell pathogenicity in autoimmune uveitis 4. Clinically, MTFR1 is significantly elevated in multiple cancers and promotes aggressive phenotypes. In lung adenocarcinoma, MTFR1 overexpression drives cisplatin resistance through p-AKT and p-ERK/P38 signaling pathways and is an independent risk factor for unfavorable prognosis 5. In tongue squamous cell carcinoma, the SNHG1/miR-194-5p/MTFR1 axis promotes epithelial-mesenchymal transition and metastatic behaviors 6. MTFR1 also emerges as a lymphoma radiotherapy-resistance gene 7.