The EGF receptor family comprises several related receptor tyrosine kinases that are frequently overexpressed in a variety of carcinomas. Members of this receptor family include EGFR (HER1), Neu (ErbB-2, HER2), ErbB-3 (HER3) and ErbB-4 (HER4), which form either homodimers or heterodimers upon ligand binding. The gene encoding ErbB-4 is expressed as a full-length protein, which produces a short membrane-anchored cytoplasmic domain fragment and a long ectodomain fragment. The short fragment is heavily tyrosine phosphorylated and possesses tyrosine kinase catalytic activity toward an exogenous substrate. Proteolytic cleavage of ErbB-4 is promoted by the binding of heregulin. ErbB-4 is involved in cell proliferation and differentiation and its expression is highest in breast carcinoma cell lines, normal skeletal muscle, heart, pituitary, brain and cerebellum. Its expression in breast cancer, pediatric brain cancer and other types of carcinomas has been reported in studies which suggest ErbB4 expression is involved in both normal tissue development and carcinogenesis.