CSTF2 (cleavage stimulation factor subunit 2) is an RNA-binding protein essential for 3'-end cleavage and polyadenylation of mammalian pre-mRNAs 1. The protein contains an RNA recognition motif (RRM) that binds to downstream U- or G/U-rich sequences through electrostatic interactions, which are the dominant factor in RNA binding 2. Beyond its canonical role in mRNA processing, CSTF2 functions as an m6A regulator that co-transcriptionally controls m6A modification by slowing RNA polymerase II elongation during transcription 3. The protein regulates alternative polyadenylation by shortening 3' untranslated regions, which can lead to loss of m6A modification sites and affect mRNA stability 4. CSTF2 is overexpressed in multiple cancers including hepatocellular carcinoma, pancreatic cancer, and breast cancer, where it promotes tumor progression 5. In hepatocellular carcinoma, CSTF2 supports hypoxia tolerance by enhancing glycolysis through PGK1 upregulation 4. The protein also suppresses anti-tumor immunity in pancreatic cancer by inhibiting innate αβ T cell infiltration 6. A missense mutation (D50A) in CSTF2's RRM domain causes X-linked intellectual disability by altering polyadenylation sites in over 1300 brain development genes 1. CSTF2 interacts with the polyadenylation machinery and ADAR1, suggesting roles in epitranscriptomic regulation 7.