TUFM (Tu translation elongation factor, mitochondrial) is a GTPase that functions as a mitochondrial translation elongation factor, promoting GTP-dependent aminoacyl-tRNA binding during protein synthesis 1. Beyond its canonical role in mitochondrial translation, TUFM plays critical roles in mitophagy and innate immunity regulation. TUFM recruits autophagy machinery (ATG5-ATG12) and innate immune regulators (NLRX1) at mitochondria, serving as a checkpoint for RIG-I-mediated antiviral signaling 2. TUFM functions as a critical hub in pathogenic mechanisms: viral proteins (influenza PB1-F2 and SFTSV nucleoprotein) exploit TUFM-mediated mitophagy to suppress MAVS-dependent type I interferon production and evade antiviral immunity 34. Post-translational modifications regulate TUFM function—lactylation at K286 following traumatic brain injury inhibits TUFM-Tomm40 interaction, suppressing mitophagy and increasing neuronal apoptosis 5, while deacetylation in NASH promotes ClpXP-mediated degradation, impairing mitophagy and activating NLRP3 inflammasome 6. Mutations in TUFM associate with combined oxidative phosphorylation deficiency 4, and genome-wide studies identify TUFM as a causal immune-genetic regulator of aging traits 7. These findings establish TUFM as a multifunctional protein integrating metabolic, immune, and mitophagic pathways.