METTL2B is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes N(3)-methylcytidine (m3C) modification at position 32 of the anticodon loop, primarily targeting tRNA(Thr)(UGU) and tRNA(Arg)(CCU) 1. This modification is part of the broader tRNA methylation pathway essential for proper tRNA function 1. METTL2B operates within a multi-enzyme system alongside METTL2A and METTL6, which employ mutually exclusive substrate selection mechanisms to ensure specificity among different tRNA species 1. Beyond its canonical tRNA modification role, METTL2B has emerged as a disease-relevant gene implicated in neurodegeneration and cancer. It was identified as a network gene potentially linking Alzheimer's disease pathogenesis in Down Syndrome through connections with APP processing and tau post-translational modification 2. In cancer biology, METTL2B is recognized as a prognostic biomarker and potential oncogene: it was incorporated into RNA processing-related prognostic signatures for gastric cancer 3, identified in mitochondrial RNA modification signatures for lower grade glioma prognosis 4, and demonstrated elevated expression in ovarian cancer where METTL2B knockdown suppressed oncogenic behaviors by inhibiting the mTOR/AKT signaling pathway 5. METTL2B's expression correlates negatively with immune cell infiltration in tumors, suggesting complex roles in tumor immunobiology 5.