EAF2 (ELL associated factor 2) is a tumor suppressor that functions as a transcriptional transactivator of RNA polymerase II elongation factors, including ELL and ELL2 12. Beyond its role in transcription elongation, EAF2 exerts potent growth-inhibitory effects through multiple mechanisms. Mechanistically, EAF2 suppresses prostate cancer through several interconnected pathways. It co-regulates STAT3 activation with p53; concurrent loss of both genes activates STAT3 signaling and drives tumorigenesis 12. EAF2 modulates androgen receptor signaling by regulating FOXA1 protein levels, thereby suppressing AR-target gene expression and cell proliferation 3. Additionally, EAF2 mediates androgen-dependent DNA repair through Ku70/Ku80 recruitment, protecting cells from DNA damage 4. EAF2 also suppresses hypoxia-induced HIF-1α activity by disrupting CBP/p300 recruitment 5. EAF2 protein stability is regulated by SIAH2-mediated polyubiquitination, which ELL1 can counteract 6. Pirin interacts with EAF2 and reduces its protein levels, alleviating growth inhibition 7. Clinically, EAF2 downregulation is frequent in advanced prostate cancer and correlates with high Gleason scores and increased tumor-associated macrophage infiltration via MIF upregulation 8. Combined EAF2 and p53 inactivation drives prostate carcinogenesis in mouse models 2, establishing EAF2 as a critical prostate tumor suppressor.