MUC20 is a transmembrane mucin glycoprotein that functions as a regulatory molecule in epithelial tissues and disease contexts. Primary function: MUC20 serves as a cell surface-associated mucin expressed in ocular surface epithelium, respiratory airways, and renal tubular cells, where it maintains epithelial homeostasis 12. Mechanism: MUC20 negatively regulates MET signaling by interacting with the MET receptor to modulate downstream RAS activation 3. In multiple myeloma, MUC20 suppresses MET-dependent activation of CDKN2A expression, thereby promoting cuproptosis and sensitivity to proteasome inhibitors 4. Conversely, in gastric cancer, intracellular MUC20 variant 2 maintains mitochondrial calcium homeostasis and enhances chemoresistance 5. Disease relevance: MUC20 downregulation correlates with active ulcerative colitis and predicts proteasome inhibitor resistance in multiple myeloma 64. Loss of MUC20 exacerbates kidney fibrosis by increasing pyroptosis via the cGAS-STING-NLRP3 axis 3. Clinical significance: A MUC4/MUC16/MUC20 signature associates with poor prognosis in pancreatic, colon, and stomach cancers 7. Paclitaxel induces MUC20 upregulation to promote esophageal cancer apoptosis through mTOR signaling 8.