EPHA4 is a receptor tyrosine kinase that binds membrane-bound ephrin to induce bidirectional signaling into neighboring cells. EPHA4 regulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. It plays an important role in the development of the nervous system, controlling different steps of axonal guidance including the establishment of the corticospinal projections. It may also control the segregation of motor and sensory axons during neuromuscular circuit development. It is also involved in synaptic plasticity, injury repair, and angiogenesis in the central nervous system. In amyotrophic lateral sclerosis and other neurodegenerative diseases, EPHA4 plays an important role in the degeneration of neurons and in disease progression, and is a putative therapy target. In immunohistochemistry, EPHA4 has highest cytoplasmic positivity in the brain, and it is also found in the thyroid, respiratory epithelial cells in the lung, reproductive tissues, skin, immune tissues, and at lower levels elsewhere. References: J Neurosci. 2011 Dec 14;31(50):18364-80, PMID: 22171039; J Neurosci. 2007 Dec 19;27(51):14205-15, PMID: 18094260; J Neurochem. 2010 Apr;113(1):153-65; Cell Chem Biol. 2017 Mar 16;24(3):293-305, PMID: 28196613