PRMT6 is a Type I protein arginine methyltransferase that catalyzes asymmetric dimethylarginine (aDMA) formation on histone and non-histone substrates. It mediates asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a), a mark associated with transcriptional repression that is mutually exclusive with activating H3K4 methylation. PRMT6 also regulates DNA base excision repair by methylating DNA polymerase beta, enhancing its binding and processivity. Beyond histones, PRMT6 methylates diverse non-histone proteins including STAT3, RCC1, and p62, influencing their localization, activation, and protein-protein interactions. Clinically, PRMT6 dysregulation contributes to multiple cancer types. In acute myeloid leukemia, PRMT6 maintains leukemia stem cells by suppressing the lipid transporter MFSD2A 1. In glioblastoma stem cells, the CK2-PRMT6-RCC1 axis drives proliferation and radiotherapy resistance, and PRMT6 inhibition with EPZ020411 enhances radiosensitivity 2. In breast cancer, PRMT6-mediated methylation of STAT3 at arginine 729 promotes metastasis, and EPZ020411 reduces metastatic dissemination 3. Lung cancer cells depend on PRMT6-catalyzed methylation of metabolic enzymes 6PGD and ENO1 for glycolysis and oxidative pentose phosphate pathway flux 4. In colorectal cancer, elevated PRMT6 suppresses tumor suppressor expression via H3R2me2a 5. PRMT6 inhibitors including EPZ020411 represent a therapeutic strategy across multiple malignancies, positioning PRMT6 as a cancer drug target 6.