EphA5, also known as Ehk1, Bsk, Cek7, Hek7, and Rek7, is a member of the Eph receptor tyrosine kinase family which binds members of the Ephrin ligand family (1 - 4). The A and B class Eph proteins have a common structural organization. Activation of kinase activity occurs after membrane-bound or clustered ligand recognition and binding. Reverse signaling is propagated through the Ephrin ligand. The mouse EphA5 cDNA encodes an 877 amino acid (aa) precursor that includes a 26 aa signal sequence, a 386 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 444 aa cytoplasmic domain (5). The ECD contains an N-terminal globular domain, a cysteine-rich domain, and two fibronectin type III domains. The cytoplasmic domain contains a juxtamembrane motif with two tyrosine residues, which are the major autophosphorylation sites, a kinase domain, and a conserved sterile alpha motif (SAM) (5). Taking into account differences in splice variants between species, comparable regions of the mouse EphA5 ECD share greater than 97% aa sequence identity with bovine, human, and rat EphA5, and 27 - 43% aa identity with mouse EphA1, 2, 3, 4, 6, 7, and 8. Multiple EphA5 splice variants exist and differ in their extracellular and intracellular sequences (5). Mouse EphA5 is expressed exclusively in brain with the highest levels in the hippocampus and limbic system (5). During embryonal development, EphA5 is preferentially expressed in neurons migrating away from the ventricular zone (5). The interaction of EphA5 with its ligands is also involved in the topographic projection of hippocampal, olfactory, and retinotectal neurons (6). Interference in this system by the transgenic expression of soluble EphA5 implicates hippocampal post-synaptic areas for native EphA5 function (7).