WDR4 is a non-catalytic scaffold subunit of the METTL1-WDR4 methyltransferase complex that catalyzes N7-methylguanine (m7G) formation in transfer RNAs and other RNA species 12. Within this complex, WDR4 serves as a tRNA-binding scaffold that positions substrates for methylation at position 46 (m7G46) in tRNAs containing the 5'-RAGGU-3' motif within the variable loop 3. This modification stabilizes tRNA tertiary structure and protects tRNAs from decay 12. WDR4 also facilitates m7G modification of specific mRNAs and miRNAs 1. Beyond its role in the METTL1 complex, WDR4 independently regulates selective mRNA translation through direct interaction with eIF4E2, promoting cholesterol efflux in tumor-associated macrophages 4. Dysregulation of WDR4 is clinically significant in multiple cancers. WDR4 upregulation promotes lenvatinib resistance in hepatocellular carcinoma and resistance to immunotherapy in breast cancer 56. WDR4 overexpression enhances translation of oncogenic transcripts including EGFR pathway genes, driving cancer progression 7. Additionally, WDR4 mutations cause developmental disorders including Galloway-Mowat syndrome 6 and microcephaly 2. Loss of METTL1-WDR4 function impairs cellular senescence prevention and accelerates aging phenotypes by reducing tRNA stability and translation efficiency 8.