Eph/ephrin signaling regulates a variety of biological processes during embryonic development including the guidance of axon growth cones,[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.

Eph receptors in turn are classified as either EphAs or EphBs based on their binding affinity for either the ephrin-A or ephrin-B ligands.

[11] During the development of the central nervous system Eph/ephrin signaling plays a critical role in the cell–cell mediated migration of several types of neuronal axons to their target destinations.

[20][21] In particular, Ephrin-B2 and EphB4 determine the arterial and venous fate of endothelial cells, respectively, though regulation of angiogenesis by mitigating expression in the VEGF signalling pathway.

Based on observations in Ephrin-A2 deficient mice, Ephrin-A2 may function in forward signalling in tumor angiogenesis; however, this ephrin does not contribute to vascular deformities during development.

[27] Recent studies with knockout mice have also shown evidence of the ephrin-eph interaction indirect role in the suppression of colorectal cancer.

Mice with APC mutation, without ephrin-B protein lack the means to prevent the spread of ephB positive tumor cells throughout the crypt-villi junction.

Although the mechanisms by which "reverse" signaling occurs are not completely understood, both ephrin-As and ephrin-Bs have been shown to mediate cellular responses that are distinct from those associated with activation of their corresponding receptors.