TRMT112 is a tRNA methyltransferase activator that enhances the catalytic activity of multiple methyltransferases involved in ribosomal and transfer RNA modification. As a regulatory subunit, TRMT112 forms heterodimeric complexes with enzymatic partners to stabilize them and enable their function. With BUD23, it catalyzes N(7)-methylation of guanine in 18S rRNA 1. Together with METTL5, TRMT112 directs N6-methyladenosine modification at position 1832 of 18S rRNA 2. The TRMT112–THUMPD3 complex catalyzes N2-methylguanosine formation at position 6 of multiple tRNA species, supporting optimal protein synthesis and cell proliferation 3. TRMT112 also cooperates with N6AMT1/HEMK2 to methylate the translation release factor eRF1 and histone H4. In nasopharyngeal carcinoma, elevated METTL5–TRMT112-mediated m6A modification at 18S rRNA position 1832 promotes ribosome assembly and selective translation of oncogenic pathways, including stabilization of mutant p53 4. In pancreatic cancer, WBSCR22–TRMT112 synergistically suppresses proliferation and invasion by transcriptional downregulation of ISG15 5, while THUMPD3–TRMT112-mediated tRNA m2G modification sustains autophagy and cancer cell growth by promoting TFEB translation 6. These findings suggest TRMT112-dependent RNA modification pathways represent therapeutic targets in multiple cancer types.