EpCAM/TROP1. Epithelial Cellular Adhesion Molecule (EpCAM), also known as KS1/4, gp40, GA733-2, 17-1A, and TROP‑1, is a 40 kDa transmembrane glycoprotein that consists of a 242 amino acid (aa) extracellular domain with two EGF‑like repeats, a 23 aa transmembrane segment, and a 26 aa cytoplasmic domain (1). Human and mouse EpCAM share 82% aa sequence identity. During embryonic development, EpCAM is detected in fetal lung, kidney, liver, pancreas, skin, and germ cells. In adults, human EpCAM is expressed on basolateral cell membranes of all simple, pseudo-stratified, and transitional epithelia but not on normal squamous stratified epithelia, mesenchymal tissue, muscular tissue, neuro-endocrine tissue, or lymphoid tissue (2). It is additionally expressed on undifferentiated embryonic stem cells, thymocytes, and dendritic cells (3-5). It is up-regulated on actively proliferating epithelial tissues, during adult liver regeneration, and on many epithelial cell-derived carcinomas (2, 6). EpCAM functions as a homophilic cell adhesion molecule (7). It associates into tetramers and forms complexes in cis with Claudin-7, CD44v6, TSPAN8, CD9, Integrin alpha 3, and Annexin A1 (8-11) that can interfere with cell adhesion (12, 13). Proteolytic cleavage of EpCAM releases multiple fragments from the ECD as well as a cytoplasmic fragment that can regulate gene transcription (14-16).