PURB (purine-rich element binding protein B) is a dual DNA/RNA-binding transcriptional regulator that functions as both an activator and repressor depending on cellular context 1. As a repressor, PURB binds purine-rich DNA elements to silence lineage-specific genes, including ACTA2 and MYOCD in smooth muscle cells, and participates in long-term silencing of tissue-specific genes through a complex with Cbx1 and Sp3 that recruits polycomb repressive machinery 2. PURB also acts as a corepressor of p53-dependent transcription in a promoter-specific manner, recognizing unique DNA elements at targets like p21 via interaction with the lncRNA HOTAIR and the EZH2 histone methyltransferase 1. Clinically, PURB dysregulation is implicated in multiple malignancies. PURB is overexpressed in human cancers and promotes ovarian cancer progression through repression of DDB2, activating oncogenic TGF-β signaling 3. Conversely, circUGP2-mediated PURB activation of ADGRB1 suppresses intrahepatic cholangiocarcinoma by stabilizing p53 4. PURB deletions at chromosome 7 occur in myelodysplastic syndrome and acute myelogenous leukemia, particularly concurrent with PURA deletions, suggesting roles in myeloid development 5. Additionally, PURB inhibition by bacterial tsRNA impairs osteogenesis 6, indicating broader physiological significance beyond cancer contexts.