ErbB-4 is a receptor tyrosine kinase that is activated by the binding of specific growth factors to its ectodomain. In addition to the initiation of signal transduction pathways that direct cell responses, such as proliferation or differentiation, this receptor is subject to ligand-dependent trafficking events. The signal transduction events are controlled by ligand-dependent activation of the receptor tyrosine kinase activity, which results in receptor autophosphorylation and the tyrosine phosphorylation of other cellular proteins. The trafficking events include migration into and out of membrane microdomains, entry into internalization pathways and endocytosis, plus proteolytic fragmentation.