Epigen is an eipthelial mitogen that belongs to the EGF superfamily (1). Mouse Epigen cDNA encodes a 153 amino acid (aa) residue type I transmembrane precursor protein with a 18 aa putative signal peptide, a 92 aa extracellular domain, a 20 aa transmembrane domain, and a 22 aa cytoplasmic domain. Expression of mouse Epigen has been detected in multiple tissues including testis, liver and heart. Over the entire protein, mouse Epigen shares from approximately 23-33% sequence homology with other EGF family members. The functional internal peptide containing the EGF motif however is more than 40% homologous with that of TGF-alpha and epiregulin. A human cDNA clone encoding a mouse epigen-like protein has also been identified (2). Similarly to other EGF family proteins, a soluble form of mouse Epigen can most likely be generated from the membrane-bound form by proteolytic cleavage. Although recombinant mouse Epigen has been shown to be mitogenic for fibroblasts (3) and epithelial cells (1), compared to EGF and TGF-alpha, it is much less potent. The EGF receptor ErbB1 can be activated upon mouse Epigen activation. Nevertheless, involvements of additional ErbB receptors in mouse Epigen signaling have not been ruled out.