EPHB2 is a receptor tyrosine kinase that binds transmembrane ephrin-B family ligands residing on adjacent cells. This leads to contact-dependent bidirectional signaling into neighboring cells. EPHB2 has important functions in axon guidance during development, and participates in the guidance of commissural axons that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. It is also involved in the guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, EPHB2 regulates dendritic spine development and maturation and stimulates the formation of excitatory synapses. EPHB2 also controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. In breast cancer, EPHB2 expression is positively correlated with HER2 expression. Furthermore, localization of EPHB2 is associated with survival; cytoplasmic positivity in cancer cells may be predictive of poor prognosis while primarily membranous staining may indicate better overall recurrence-free survival. In immunohistochemistry, EPHB2 has membranous and cytoplasmic positivity in many tissues throughout the body. It is found in neurons throughout the brain, with high positivity in the cerebral cortex, hippocampus, basal ganglia and cerebellum. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Oncotarget. 2016 Apr 19;7(16):21362-80, PMID: 26870995;