Epithelial Cell Adhesion Molecule (EpCAM) is a signal type I transmembrane glycoprotein that belongs to the EPCAM family. EpCAM is composed of an extracellular domain with one thyroglobulin type-1 domain, a transmembrane domain and a cytoplasmic domain. EpCAM is found on the surface of adenocarcinoma, but not on mesodermal or neural cell membranes. The EpCAM molecule has been shown to function as a homophilic Ca2+ independent adhesion molecule. It may act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium as an immunological barrier providing the first line of defense against infection. Defects in EPCAM are a cause of hereditary non-polyposis colorectal cancer type 8 (HNPCC8) and diarrhea type 5 (DIAR5). EpCAM plays a role in embryonic stem cells proliferation and differentiation; it up-regulates the expression of FABP5, MYC and Cyclin A and Cyclin E. It is highly and selectively expressed by undifferentiated embryonic stem cells.