OSGEPL1 is a mitochondrial acyltransferase essential for synthesizing threonylcarbamoyladenosine (t6A37), a universal tRNA modification at position 37 of adenosine-decoding tRNAs 1. OSGEPL1 catalyzes transfer of the threonylcarbamoyl moiety from threonylcarbamoyl-AMP (TC-AMP), synthesized by YrdC, to five mitochondrial tRNAs including tRNAThr, tRNALys, tRNAIle, and tRNASer 2. The enzyme recognizes specific tRNA nucleotide sequences, utilizing C34 as an anti-determinant, and its activity is modulated by post-translational acetylation and CO2/bicarbonate availability 12. t6A37 modification stabilizes anticodon stem-loop structure and maintains translational accuracy 3. OSGEPL1 deletion impairs mitochondrial tRNA aminoacylation and causes codon misreading, triggering mitochondrial dysfunction and unfolded protein response, though remaining non-essential for baseline viability 4. Dysregulation associates with multiple pathologies including cancer (high OSGEPL1 expression predicts favorable ovarian cancer prognosis), neurodegenerative disease (FXTAS modifier), and lung transplant complications 567. OSGEPL1 mutations cause mitochondrial disease with translational defects 2.