MTRF1L (mitochondrial translation release factor 1 like) is a mitochondrial peptide chain release factor that directs translation termination in response to stop codons UAA and UAG in the mitochondrial matrix. The protein functions as part of the mitochondrial translational termination phase, working alongside other mitochondrial translation factors (mtIF2, mtIF3, mtEFTu, mtEFTs, mtEFG1) to coordinate protein synthesis from mtDNA-encoded genes 1. MTRF1L contains a conserved GGQ motif that undergoes glutamine methylation by the enzyme HEMK1, a modification also conserved in bacterial release factors, though this specific methylation appears dispensable for basic cell growth and mitochondrial protein homeostasis under standard culture conditions 2. Functionally, MTRF1L expression correlates with exercise-induced mitochondrial biogenesis in skeletal muscle and is downregulated during muscle denervation-induced atrophy, indicating its role in mitochondrial biogenesis and integrity 1, 3. Clinically, MTRF1L has emerged as a potential biomarker in disease contexts: it shows causal association with colorectal cancer (CRC) risk and improved prognosis when highly expressed, with associations to multiple immune cell types 4. Additionally, MTRF1L is identified as a diagnostic hub gene in sarcopenia, connecting mitochondrial dysfunction and immune disorders 5. The protein also exhibits novel protein-protein interactions, including partnerships with LYRM1 6.