MUC15 is a heavily glycosylated transmembrane mucin protein localized to the plasma membrane and Golgi lumen with dual roles in cancer biology. Primary function involves cell adhesion and glycocalyx regulation: MUC15 localizes to focal adhesions and interacts with integrins, with its ectodomain architecture governing integrin clustering states and adhesion transitions 1. The protein is abundantly expressed in placenta, salivary gland, thyroid, trachea, esophagus, and kidney 2. MUC15 exhibits context-dependent functions across cancer types. In esophageal squamous cell carcinoma and pancreatic cancer, MUC15 acts as a tumor suppressor, with reduced expression correlating with worse prognosis and enhanced immune infiltration [PMID:40225867; 32]. Conversely, in colorectal cancer, MUC15 overexpression enhances proliferation, invasion, and colony formation through ERK1/2 activation 4. MUC15 undergoes frameshift mutations in microsatellite-instable gastric and colorectal cancers (14.7% and 15.2% respectively), with expression loss common in affected tumors 5. Clinically, MUC15 polymorphisms associate with hepatocellular carcinoma capsule formation, affecting prognosis 6. In preeclampsia, placental MUC15 protein is significantly elevated and cleaved by matrix metalloproteinases, potentially reflecting protective mechanisms in placental dysfunction 7.