ErbB4 is a member of the receptor tyrosine kinase family of proteins. The four members of this family are ErbB1 (Epidermal growth factor receptor; EGFR/HER1), ErbB2 (HER2/Neu), ErbB3 (HER3), and ErbB4 (HER4). The ErbB receptor members are single-pass transmembrane proteins with an extracellular ligand-binding domain and a cytoplasmic tyrosine-kinase domain. The epidermal growth factor (EGF) and its related proteins serve as the ligands for the ErbB receptors. Upon binding, the receptors homo- or heterodimerize, autophosphorylate and make contact with adapter molecules to transmit cellular signals involved in cell proliferation, survival, and differentiation. The ligands preferred by ErbB4 include neuregulins (NRG-2 and NRG-3), heparin-binding EGF-like growth factor, and betacellulin, and epiregulin. ErbB4 appears to be important to mammary gland development and lactation; however its role in breast cancer has not been unequivocally determined.