METTL16 is an RNA N6-methyladenosine (m6A) methyltransferase that plays critical roles in both transcriptional and post-transcriptional regulation. The protein functions as an m6A writer, depositing methylation marks on hundreds of specific mRNA targets in the nucleus, while also serving as a translation-initiation facilitator in the cytoplasm through direct interactions with eukaryotic initiation factors and ribosomal RNA 1. Unlike the METTL3-METTL14 complex, METTL16 has substrate specificity requiring both sequence motifs and specific RNA structures for methylation activity 2. The protein undergoes post-translational modifications including lactylation at K229 and K269, which enhances its function in various cellular contexts 34. METTL16 demonstrates significant disease relevance across multiple cancer types, promoting tumorigenesis in hepatocellular carcinoma, acute myeloid leukemia, and colorectal cancer through diverse mechanisms including metabolic reprogramming of branched-chain amino acid metabolism and glycolysis 567. In hepatocellular carcinoma, METTL16 confers ferroptosis resistance through the SENP3-LTF signaling axis 7. The protein's essential role in cancer cell survival and its involvement in therapeutic resistance make it an attractive target for cancer treatment 8.