LCMT2 (leucine carboxyl methyltransferase 2) is a probable S-adenosyl-L-methionine-dependent methyltransferase that functions as a component of the wybutosine biosynthesis pathway, catalyzing methylation reactions in tRNA modification 1. Wybutosine and its derivative hydroxy-wybutosine (OHyW) are hypermodified guanosines located at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA, essential for proper tRNA function and protein synthesis fidelity. Clinically, LCMT2 shows significant disease relevance in hematologic malignancies. Expression levels of LCMT2 are significantly decreased in acute myeloid leukemia (AML) compared to myelodysplastic syndromes (MDS), with lower LCMT2 expression correlating with reduced drug sensitivity and limited differentiation potential in AML cell lines 1. Additionally, LCMT2 was identified as one of six independent prognostic genes in a tRNA modification-related signature predicting survival outcomes and treatment response in clear cell renal cell carcinoma 2. Frameshift mutations in LCMT2 occur in colorectal cancers with high microsatellite instability (MSI-H), suggesting potential tumor suppressor functions 3. These findings highlight LCMT2's pivotal role in tRNA biology and suggest therapeutic potential through targeted modulation of tRNA modification pathways in cancer treatment.