PRMT5 is a protein arginine methyltransferase that catalyzes the formation of monomethylarginine and symmetrical dimethylarginine (sDMA) residues on target proteins. It plays essential roles in RNA processing—specifically in spliceosomal snRNP assembly through methylation of Sm proteins—and in transcription regulation through histone modifications and interactions with RNA polymerase II. PRMT5 also attenuates growth factor signaling by methylating components of the EGFR-MAPK pathway and regulates cellular proliferation through effects on cyclin E1. Beyond these canonical functions, PRMT5 has emerged as a key driver of cancer progression across multiple tumor types. In high-grade serous ovarian cancer, elevated PRMT5 maintains chemoresistance by transactivating stress response genes 1. In breast cancer with RB1 loss, PRMT5 inhibition blocks G1-to-S transition through effects on FUS and RNA polymerase II, and the inhibitor pemrametostat shows synergistic activity with fulvestrant 2. PRMT5 also suppresses ferroptosis by stabilizing GPX4 through methylation, preventing its ubiquitin-mediated degradation 3, and promotes metastasis via AKT methylation 4. A clinically actionable vulnerability exists in MTAP-deleted cancers, where accumulation of the metabolite methylthioadenosine specifically inhibits PRMT5, creating dependence on PRMT5 function 56. PRMT5 inhibitors including pemrametostat demonstrate activity in adenoid cystic carcinoma 7, pancreatic cancer 8, and MTAP-deleted tumors when combined with immune checkpoint blockade 9. PRMT5 also constrains antitumor immunity by methylating components of innate immune pathways; inhibition enhances immunotherapy efficacy 10.