ARID3B is a DNA-binding transcription factor that functions as a chr15 remodeler with context-dependent roles in cancer and development. As a nuclear protein, ARID3B forms complexes with ARID3A and histone demethylase KDM4C to regulate transcription through chr15 modification 1. In this complex, ARID3B recruits KDM4C to reduce histone 3 lysine 9 trimethylation, promoting transcription of stemness factors 1. ARID3B directly binds E2F target genes (Cdc2, cyclin E1, p107) to regulate E2F-dependent transcription and cell cycle progression 2. Disease relevance is cancer-type dependent. In ovarian cancer and colorectal cancer, ARID3B overexpression promotes tumor progression by expanding cancer stem cell populations (CD133+, CD44+) and activating stemness genes (Notch2, LGR5, PROM1) while simultaneously upregulating PD-L1 for immune escape 3, 4. Conversely, in gastric cancer, ARID3B expression is reduced and correlates with better prognosis, where overexpression suppresses proliferation and migration 5. In non-small cell lung cancer, ARID3B directly regulates oncogenic lncRNAs MALAT1 and NORAD 6. Beyond cancer, ARID3B variants confer cleft lip/palate susceptibility through liquid-liquid phase separation-mediated transcriptional programs 7. The let-7 microRNA suppresses ARID3B expression, linking ARID3B to stem cell differentiation and tumor suppression 1. ARID3B emerges as a pleiotropic factor whose oncogenic or tumor-suppressive function depends on tissue context.