PRMT5 is a protein arginine methyltransferase that catalyzes mono- and symmetric dimethylation of arginine residues, with preference for monomethylarginine formation 1. The enzyme functions in diverse biological processes through methylation of histone and non-histone protein substrates. Canonically, PRMT5 mediates symmetric dimethylation of small nuclear ribonucleoproteins (SNRPD1/D3), essential for snRNP biogenesis and spliceosome assembly 1. Beyond splicing, PRMT5 regulates transcription through histone H3 and H4 methylation, controls cell cycle via cyclin E1 repression, and modulates signal transduction pathways including EGF and TGF-β signaling 1. PRMT5 operates through complex formation with MEP50/WDR77 and other cofactors that regulate substrate specificity and subcellular localization 1. Clinically, PRMT5 dysregulation drives multiple cancers through substrate-specific mechanisms: it methylates AKT to promote metastasis in neuroblastoma 2, stabilizes GPX4 to suppress ferroptosis in various tumors 3, methylates SMAD4 to activate TGF-β signaling in colorectal cancer 4, and methylates FUBP1 in prostate cancer 5. MTAP-deleted cancers show synthetic lethality with PRMT5 inhibition 6, providing biomarker-directed therapeutic opportunity. PRMT5 overexpression correlates with poor prognosis across multiple malignancies 7, establishing PRMT5 inhibitors as promising targeted therapeutics combined with conventional chemotherapy.