TRMT13 is a tRNA methyltransferase that catalyzes 2'-O-methylation of cytidine at position 4 in tRNA(Pro) and tRNA(Gly)(GCC), and adenosine methylation at position 4 in tRNA(His). Beyond its canonical tRNA modification role, TRMT13 has emerged as a potential tumor suppressor in multiple malignancies. In papillary thyroid cancer (PTC), TRMT13 expression is significantly downregulated, and restoration of TRMT13 inhibits cancer cell proliferation, migration, and invasion through a mechanism involving regulation of ANAPC4 1. In nude mouse xenograft models, TRMT13 overexpression suppresses tumor growth, and TRMT13 expression levels correlate with patient survival 1. TRMT13 has also been identified as a driver gene in primary central nervous system lymphoma (PCNSL), appearing among the top 15 frequently mutated genes in this aggressive B-cell malignancy 2. Additionally, TRMT13 expression patterns contribute to identifying distinct subtypes of mild cognitive impairment, suggesting potential relevance in neurodegenerative conditions 3. These findings indicate that TRMT13 functions beyond its primary role in tRNA modification, with significant implications for cancer biology and neurological disease pathogenesis.