TRMT10A (tRNA methyltransferase 10A) is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of N1-methylguanine at position 9 (m1G9) in nuclear-encoded tRNAs 1. The enzyme localizes to the nucleolus and nucleus, where tRNA modifications occur 2. TRMT10A methylates a subset of nuclear tRNAs including tRNA-ArgCCT and initiator methionine tRNA, with loss of G9 methylation decreasing steady-state tRNA levels and altering post-transcriptional modifications 13. TRMT10A deficiency disrupts the cytosolic tRNA pool required for protein synthesis and impairs ribosome functionality at specific codons 3. Biallelic TRMT10A mutations cause an early-onset syndromic disease characterized by diabetes mellitus, microcephaly, intellectual disability, epilepsy, and short stature 24. TRMT10A deficiency induces pancreatic β-cell apoptosis and impairs brain development through disrupted translation of neuronal structural proteins 23. Recent evidence reveals TRMT10A participates in DNA damage response via phosphorylation by ATM, regulating homologous recombination repair and BRCA1 recruitment 5. Additionally, TRMT10A suppression promotes glioblastoma vasculogenic mimicry through enhanced tRNA fragment-22 generation and HIF1A upregulation 6. Clinically, TRMT10A sequencing is recommended for early-onset diabetes with intellectual disability and microcephaly, particularly in non-autoimmune, non-obese presentations 7.