PRMT3 is a type I protein arginine methyltransferase that catalyzes monomethylation and asymmetric dimethylation of arginine residues in target proteins. Beyond its established role in ribosomal protein methylation, PRMT3 regulates transcription through histone H4 arginine-3 dimethylation, promoting osteogenesis and modulating miRNA expression. It also negatively regulates retinoic acid signaling by inhibiting ALDH1A1 enzymatic activity through protein–protein interaction rather than methylation-dependent mechanisms. PRMT3 is implicated in multiple cancers through several oncogenic pathways. In hepatocellular carcinoma, PRMT3 promotes oxaliplatin resistance via IGF2BP1 methylation 1, drives glycolytic reprogramming through LDHA and PDHK1 methylation 23, and confers immunotherapy resistance by methylating HSP60 to suppress cGAS/STING-mediated anti-tumor immunity 4. In endometrial carcinoma, PRMT3 inhibition enhances ferroptosis sensitivity and synergizes with anti-PD-1 therapy and radiation 5. PRMT3 overexpression also promotes glioblastoma progression via HIF1A-mediated glycolysis 6. Clinically, PRMT3 represents a therapeutic target in multiple cancer contexts. Selective PRMT3 inhibitors (SGC707) and degrader-based approaches show efficacy in preclinical models 67, with combination strategies using immunotherapy checkpoint inhibitors or metabolic inhibitors showing enhanced anti-tumor activity.