TRMO (tRNA methyltransferase O) is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the addition of a methyl group to form N6-methyl-N6-threonylcarbamoyladenosine (m6t6A37) at position 37 of the tRNA anticodon loop, specifically in tRNA(Ser)(GCU) and tRNA(Thr) 1. This enzyme represents a novel Class VIII methyltransferase with a unique single-sheeted β-barrel structure distinct from known methyltransferase families 1. The m6t6A37 modification enhances tRNA decoding efficiency and fine-tunes translation fidelity across organisms from bacteria to mammals 1. In the absence of TRMO function, the precursor t6A is converted to cyclic t6A instead 1. Clinically, TRMO variants have been associated with differentiated thyroid carcinoma (DTC) susceptibility at chromosome 9, integrated within gene networks related to metabolism and signal transduction 2. Additionally, TRMO functions as a prognostic regulator in clear cell renal cell carcinoma, where it is part of a six-gene signature predictive of patient survival outcomes and immune microenvironment composition 3. A novel TRMO-TRNT1 fusion gene has been identified in high-grade oral squamous cell carcinoma samples, suggesting potential oncogenic relevance 4. These findings indicate TRMO's broader involvement beyond translation regulation, extending to cancer pathogenesis and progression.