TSFM encodes a mitochondrial translation elongation factor that functions as a guanine nucleotide exchange factor 1. The protein associates with EF-Tu.GDP complexes and catalyzes GDP-to-GTP exchange, then remains bound to aminoacyl-tRNA.EF-Tu.GTP complexes during the elongation phase of mitochondrial translation 1. This essential role in mitochondrial protein synthesis directly supports oxidative phosphorylation (OXPHOS) capacity. Clinically, TSFM mutations cause combined oxidative phosphorylation deficiency 3, manifesting as multisystem disease. Reported presentations include childhood-onset ataxia with hypertrophic cardiomyopathy 1, dilated cardiomyopathy with fibro-adipose replacement 2, and infantile encephalocardiomyopathy with sensorineural hearing loss 3. The heart appears particularly vulnerable to TSFM dysfunction 2. Recent evidence identifies TSFM as a potential therapeutic target in multiple sclerosis, with MS-associated SNPs affecting TSFM pre-mRNA splicing patterns 45. Brain-tissue TSFM variants show first-level evidence for MS contribution 5. Additionally, TSFM modulation through the piR-26441/YTHDC1 axis regulates mitochondrial complex I activity and OXPHOS in ovarian cancer 6. However, short-term TSFM knockdown in cultured cells did not significantly alter APP processing, ROS levels, or mitochondrial function parameters 7, suggesting complex cellular context-dependence.