MTIF2 (mitochondrial translational initiation factor 2) is a nuclear-encoded protein that functions in mitochondria as an essential component of the translation initiation machinery 1. MTIF2 protects formylmethionyl-tRNA from spontaneous hydrolysis and promotes its binding to the mitoribosomal 28S subunit, facilitating the assembly of elongation-competent 55S mitoribosomes on leaderless mRNAs 2. The protein also catalyzes GTP hydrolysis during 70S ribosomal complex formation and remains indispensable for mitochondrial protein synthesis 3. Structurally, MTIF2 contains an insertion domain critical for stabilizing interactions with mitoribosomes and proper folding 4. MTIF2 plays a critical role in synthesizing OXPHOS complex subunits encoded by mitochondrial DNA. Reduced MTIF2 levels correlate with diminished complex I and IV content and impaired oxidative capacity in cardiomyocytes 5. Physical activity upregulates MTIF2 expression, linking this factor to exercise-induced improvements in mitochondrial function 6. In hepatocellular carcinoma, MTIF2 overexpression suppresses apoptosis and immunogenic cell death through interaction with AIFM1, suggesting potential roles in cancer metabolism and chemoresistance 7. The MTIF2 gene spans approximately 33.5 kb with 16 exons and contains regulatory elements for transcription factors including Sp1 and NRF-2 1.