TRMT9B (also known as hTRM9L/KIAA1456) is a tRNA methyltransferase that modifies wobble uridines in specific arginine and glutamic acid tRNAs, functioning in both the nucleus and cytoplasm. The enzyme catalyzes tRNA (5-carboxymethyluridine(34)-5-O)-methylation as part of normal tRNA modification pathways 1. Mechanistically, TRMT9B acts as a tumor suppressor through tRNA modification-dependent mechanisms. Re-expression of TRMT9B in cancer cells suppresses tumor growth by inducing G0/G1 cell cycle arrest and promoting senescence-like phenotypes 1. This growth inhibition is linked to upregulation of the retinoblastoma-interacting protein LIN9 and suppression of HIF1-α-dependent hypoxic signaling 1. TRMT9B overexpression inhibits cell cycle progression by blocking G1/S and G2/M transitions across multiple cancer cell lines 23. Clinically, TRMT9B expression is downregulated in multiple carcinoma types including breast, bladder, colorectal, cervical, and testicular cancers 1. Loss of TRMT9B expression renders tumors sensitive to aminoglycoside antibiotics, suggesting therapeutic potential 1. These findings position TRMT9B as a candidate biomarker and therapeutic target in cancer management.