MTFR2 (mitochondrial fission regulator 2) is a key regulator of mitochondrial dynamics that promotes mitochondrial fission through interaction with the fission machinery protein DRP1 1. In normal physiology, MTFR2 facilitates aerobic respiration, particularly in testis tissue, and its downregulation impairs mitochondrial function and spermatogenesis 2. In cancer biology, MTFR2 plays a prominent oncogenic role across multiple tumor types. In hepatocellular carcinoma (HCC), elevated MTFR2 expression correlates with worse prognosis and promotes tumor progression through mitochondrial fission-dependent mechanisms 3. MTFR2 drives metabolic reprogramming via the NFYC/MTFR2/Akt signaling axis, shifting cancer cells from oxidative phosphorylation to glycolysis 4. In stromal cells, MTFR2-mediated mitochondrial fission enhances transfer of fatty acids and mitochondria to tumor cells, sustaining their metabolic demands 1. Similarly, in breast cancer, MTFR2 overexpression switches glucose metabolism from OXPHOS to glycolysis via HIF1α/HIF2α-dependent mechanisms, promoting epithelial-mesenchymal transition and tumor progression 5. MTFR2 upregulation is also associated with poor prognosis in lung adenocarcinoma and oral squamous cell carcinoma through cell cycle dysregulation and EMT pathways 6, 7. MTFR2 represents a promising therapeutic target for cancer treatment.