Eph/ephrin signaling has been implicated in the regulation of a host of processes critical to embryonic development including axon guidance,[1] formation of tissue boundaries,[2] cell migration, and segmentation.

[3] Additionally, Eph/ephrin signaling has been identified to play a critical role in the maintenance of several processes during adulthood including long-term potentiation,[4] angiogenesis,[5] and stem cell differentiation and cancer.

[10] EphA/ephrinA interaction typically occur with higher affinity than EphB/ephrin-B interactions which can partially be attributed to the fact that ephrin-As bind via a "lock-and-key" mechanism that requires little conformational change of the EphAs in contrast to EphBs which utilize an "induced fit" mechanism that requires a greater amount of energy to alter the conformation of EphBs to bind to ephrin-Bs.

[17] Segmentation is a basic process of embryogenesis occurring in most invertebrates and all vertebrates by which the body is initially divided into functional units.

Further studies then showed the role of Eph’s in topographic mapping in other regions of the central nervous system, such as learning and memory via the formation of projections between the septum and hippocampus.

[24] In addition to the formation of topographic maps, Eph/ephrin signaling has been implicated in the proper guidance of motor neuron axons in the spinal cord.

In C. elegans a knockout of the vab-1 gene, known to encode an Eph receptor, and its Ephrin ligand vab-2 results in two cell migratory processes being affected.

It is thought to distinguish arterial and venous endothelium, stimulating the production of capillary sprouts as well as in the differentiation of mesenchyme into perivascular support cells.

Mouse embryonic models show expression of EphA1 in mesoderm and pre-endocardial cells, later spreading up into the dorsal aorta then primary head vein, intersomitic vessels, and limb bud vasculature, as would be consistent with a role in angiogenesis.

Different class A Eph receptors have also been detected in the lining of the aorta, brachial arch arteries, umbilical vein, and endocardium.

[29] It is possible that the increased expression of Eph in cancer plays several roles, first, by acting as survival factors or as a promoter of abnormal growth.

[35][36] The Eph receptors were initially identified in 1987 following a search for tyrosine kinases with possible roles in cancer, earning their name from the erythropoietin-producing hepatocellular carcinoma cell line from which their cDNA was obtained.