CMTR1 (cap methyltransferase 1) is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes 2'-O-ribose methylation of the first nucleotide in mRNA cap structures, converting m(7)GpppG to m(7)GpppRm (cap1 modification) 1. This co-transcriptional capping process is enhanced by CK2-mediated phosphorylation of CMTR1, which increases its recruitment to RNA polymerase II during the G1 phase 2. CMTR1 displays preferential activity on 5' Terminal Oligopyrimidine (TOP)-motif containing transcripts, particularly those encoding ribosomal proteins and histones, making it essential for ribosome biogenesis and cell proliferation 3. Cap1 modifications mark RNAs as "self," preventing innate immune activation; loss of CMTR1 causes embryonic lethality and germline-specific infertility in mice, with adult livers showing chr6 interferon pathway activation 4. Influenza A virus exploits CMTR1-mediated cap formation through "cap snatching," requiring both functional CMTR1 and its phosphorylation for viral RNA capping and efficient replication 52. In cancer biology, CMTR1 is significantly upregulated across multiple cancer types and is required for tumor growth; CMTR1 depletion substantially inhibits tumorigenesis in breast cancer models 3. During neural differentiation, CMTR1 upregulation maintains histone and ribosomal protein expression to support DNA replication and translation 1. Novel CMTR1 inhibitors represent potential therapeutic agents for influenza treatment and cancer intervention.