TRMT6 (tRNA methyltransferase 6 non-catalytic subunit) functions as the substrate-binding component of a methyltransferase complex that catalyzes N1-methyladenosine (m1A) modifications in both tRNAs and mRNAs 1. Together with the catalytic subunit TRMT61A, TRMT6 forms a complex that methylates adenosine at position 58 in initiator methionyl-tRNA and also modifies specific mRNA sites containing tRNA T-loop-like structures 1. The complex additionally generates m1A modifications in tRNA-derived fragments (tRFs), which affects their gene-silencing activity 2. TRMT6 is significantly overexpressed across multiple cancer types, including hepatocellular carcinoma, colorectal cancer, neuroblastoma, and triple-negative breast cancer 3456. Mechanistically, TRMT6-mediated m1A modifications regulate translation efficiency of specific mRNAs, including PPARδ in liver cancer and FTH1 in breast cancer 36. The enzyme also controls histone mRNA translation through codon-biased mechanisms 4 and modulates cellular stress responses 7. High TRMT6 expression correlates with poor patient survival and promotes tumor growth, metastasis, and therapeutic resistance 34, making it an attractive target for cancer therapy.