METTL3 is the catalytic subunit of the METTL3-METTL14 heterodimeric complex that deposits N6-methyladenosine (m6A) modifications on adenosine residues within the consensus sequence 5'-[AG]GAC-3' in mRNAs and other RNAs 1 2. While METTL3 provides catalytic activity, METTL14 plays a critical structural role essential for substrate recognition 2. m6A modifications regulate mRNA stability, processing, and translation efficiency, with methylation generally promoting mRNA destabilization and degradation in the nucleoplasm 2. METTL3 also functions as a positive regulator of translation independently of its methyltransferase activity by interacting with translation initiation machinery in the cytoplasm 3. METTL3 regulates diverse biological processes including circadian rhythms, stem cell differentiation, DNA damage responses, T-cell homeostasis, and primary miRNA processing 2. Additionally, METTL3 maintains nucleoli integrity in embryonic stem cells by facilitating SUV39H1/H2 degradation through the CRL4 E3 ubiquitin ligase 4. Clinically, METTL3 overexpression correlates with poor prognosis in multiple cancers. In colorectal cancer, elevated METTL3 promotes JAK1/STAT3 signaling activation through both m6A-dependent translation enhancement and m6A-independent transcriptional regulation 5. In breast cancer, the METTL3/m6A/IGF2BP3 axis stabilizes PD-L1 mRNA, promoting immune escape 6. In tumor-infiltrating myeloid cells, lactate-driven METTL3 upregulation enhances JAK1 translation and immunosuppression 7. These findings position METTL3 as a therapeutic target in cancer immunotherapy.