WDR77 is a non-catalytic WD-repeat protein that functions as a critical component of the methylosome complex alongside PRMT5 and CLNS1A 1. The complex catalyzes symmetric dimethylation of arginine residues on histone proteins and spliceosomal Sm proteins, regulating spliceosome assembly and genome organization 2. WDR77 also facilitates PRMT5-mediated methylation of Piwi proteins required for meiotic localization 3. Beyond PRMT5 interaction, WDR77 exhibits multiple independent regulatory functions. It promotes cell-cycle progression, regulates E2F transcription factors, and modulates TGFβ signaling 4. WDR77 translocates dynamically between nucleus and cytoplasm, with subcellular localization determining its functional output 4. In cancer, WDR77 is frequently dysregulated. MTAP-deleted tumors show enhanced dependency on the PRMT5-WDR77 complex 5. WDR77 overexpression correlates with poor outcomes in breast cancer through AKT activation 6 and melanoma through CDC20-mediated cell-cycle dysregulation 7. In keloid pathogenesis, HNRNPC stabilizes WDR77 mRNA through m6A methylation, promoting fibroblast proliferation via TGFβ/SMAD3 signaling 8. Conversely, the PRMT5/WDR77 complex restricts hepatitis E virus replication by methylating viral ORF1 protein 9. These findings establish WDR77 as a multifunctional therapeutic target across diverse disease contexts.