ErbB4 is a type I membrane glycoprotein that is a member of the ErbB family of tyrosine kinase receptors. ErbB family members serve as receptors for the epidermal growth factor (EGF) family of growth factors. ErbB4 is expressed in normal skeletal muscle,heart, pituitary, brain and several breast carcinomas. ErbB4 ligands include the neuregulins, beta-cellulin and heparin-binding EGFlike growth factor (HBEGF). Monomeric ErbB4 binds its ligands with low affinity. Several ErbB4 isoforms exist. Two of these differ in the presence of juxtamembrane extracellular sequences which regulate the ability of TACE (TNFα converting enzyme) to proteolytically cleave ErbB4 from the cell surface. These isoforms exhibit tissuespecific expression. Another isoform lacks the phosphoinositide 3kinase activation sequence present in the ErbB4 cytoplasmic domain. ErbB4 appears to play important roles in neuronal development, development of the heart and cancer.