EphA4 is a member of the Eph receptor tyrosine kinase family.

Eph receptors are subdivided into two subclasses, termed EphA and EphB, based on sequence similarity and their preference for binding a particular subclass of ephrins. The domain organization of Eph receptors contains a globular ligand binding domain (LBD), a cysteine-rich region, and two fibronectin type III domains (FN1 and FN2). It also contains a transmembrane (TM) helix, and an intracellular part consisting of a juxtamembrane (JM) region and a tyrosine kinase domain. Eph kinase activity is auto-inhibited through interaction with its own JM region, this auto inhibition is released by phosphorylation¹.

Interactions of Eph receptors with their ligands, ephrins, at cell-cell interfaces promote a variety of cellular responses, including repulsion, attraction and migration².

EphA4 is activated by all members of the ephrin-A ligand family and most members of the ephrin-B family¹. Upon ligand binding it activates pathways that regulate the formation of the axon tract and cortical network as well as radial migration of cortical neurons in the cortex³.

EphA4 is expressed in the neural ectoderm at embryonic day 8 and then in various cell types throughout the cortex during subsequent stages of neurodevelopment⁴, its major effect on cell-cell interfaces makes this receptor highly important for the study of cellular regeneration and various types of disease.