POU2F1 (POU class 2 homeobox 1) is a transcription factor that functions as a master regulator of metabolic reprogramming and epithelial-to-mesenchymal transition in multiple cancer types. As a DNA-binding transcription factor, POU2F1 directly binds promoter regions to activate target gene expression, including ALDOA in colon cancer and the miR-29 cluster in gastric cancer 1 2. Beyond cancer, POU2F1 participates in viral infection responses by forming multiprotein-DNA complexes with HSV VP16 and HCFC1 to enable viral immediate early gene transcription, and regulates pigmentation by modulating expression of genes including MC1R and MITF 3. In cancer pathogenesis, POU2F1 overexpression promotes proliferation, glycolytic metabolism, and the pentose phosphate pathway, while suppressing oxidative stress and apoptosis 1. POU2F1 drives hepatocellular carcinoma progression through AKT pathway-dependent activation of epithelial-to-mesenchymal transition genes (Twist1, Snai1, Snai2, ZEB1), correlating with poor prognosis 4. Notably, tRNA-derived fragment tRF-18-HSQS52D2 suppresses POU2F1 expression post-transcriptionally, reducing colorectal cancer malignancy 5. High POU2F1 expression associates with chemoresistance, advanced tumor stage, and metastasis across multiple cancer types, establishing it as a therapeutic target.