METTL1 is the catalytic component of the METTL1-WDR4 methyltransferase complex that generates N7-methylguanosine (m7G) modifications in various RNA species 1. The complex primarily catalyzes m7G46 formation in tRNAs containing the 5'-RAGGU-3' motif within the variable loop, which stabilizes tRNA tertiary structure and protects against degradation 12. Structurally, WDR4 serves as a scaffold while METTL1's N-terminal region forms part of the catalytic pocket, with methyltransferase activity regulated by S27 phosphorylation 2. Beyond tRNAs, METTL1 methylates specific microRNAs like let-7, promoting their processing by disrupting inhibitory secondary structures in pri-miRNAs 3. The enzyme also modifies circRNAs, preventing their degradation and affecting downstream signaling pathways 4. METTL1 dysregulation has significant disease implications, being frequently amplified in cancers where it drives oncogenic transformation through enhanced translation of growth-promoting proteins 5. It promotes lenvatinib resistance in hepatocellular carcinoma by upregulating EGFR pathway genes 6 and contributes to cardiac hypertrophy by regulating SRSF9-mediated splicing 7. These diverse functions position METTL1 as a promising therapeutic target across multiple pathological conditions.