MED28 is a Mediator complex subunit that functions as a coactivator for RNA polymerase II-dependent transcription, serving as a bridge between gene-specific regulatory proteins and basal transcription machinery. Beyond its nuclear role in transcriptional regulation, MED28 interacts with NF2/merlin in cytosolic signaling pathways affecting the actin cytoskeleton 1. MED28 promotes cancer progression through multiple mechanisms. It enhances epithelial-mesenchymal transition (EMT) and cell migration in colorectal and lung cancers by upregulating matrix metalloproteinase 2 (MMP2) and activating Wnt/β-catenin signaling 23. In breast cancer, MED28 regulates migration via MEK1-dependent pathways 4. MED28 overexpression shortens the cell cycle and induces genomic instability through increased aneuploidy and micronucleus formation 5. In liver cancer, elevated MED28 expression correlates with poor prognosis and drives proliferation through AKT/mTOR signaling 6. Clinically, MED28 overexpression is documented across multiple cancer types, suggesting its value as a therapeutic target. Bioactive vitamin D (calcitriol), resveratrol, and apigenin suppress MED28 expression and attenuate cancer cell growth and migration 276. Additionally, MED28 is essential for embryonic development and pluripotency maintenance 1, indicating broad developmental significance beyond cancer biology.