YTHDF2 is an RNA-binding protein that recognizes N6-methyladenosine (m6A)-modified RNAs and primarily functions to regulate mRNA stability and decay. The protein contains a C-terminal YTH domain that selectively binds m6A-containing mRNAs, while its N-terminal domain localizes bound transcripts to cellular RNA decay sites such as processing bodies 1. YTHDF2 targets over 3,000 cellular RNAs, predominantly mRNAs with a conserved G(m6A)C motif, and promotes their degradation by relocating them from the translatable pool to mRNA decay sites 1. Beyond its canonical m6A reader function, YTHDF2 also acts as a 5-methylcytosine (m5C) reader, where it stabilizes certain mRNAs by recruiting PABPC1, demonstrating dual RNA modification recognition capabilities 2. In cancer contexts, YTHDF2 plays complex roles: it promotes tumor progression in hepatocellular carcinoma by stabilizing cell cycle transcripts MCM2 and MCM5 3, facilitates immune evasion in B cell malignancies 2, and regulates tumor-associated macrophage reprogramming 4. YTHDF2 also suppresses innate immunity by sequestering m6A-modified circular RNAs, preventing their recognition by pattern recognition receptors 5. These findings establish YTHDF2 as a critical regulator of RNA metabolism with significant implications for cancer therapy and immune responses.