Ephrin type-A receptor 3 (EPHA3), a member of the EphA receptor subclass, controls cell fate, cell shape, cell communication, axon guidance, and the embryonic development of vital organs like the brain, heart, lungs, and kidney. For example, EPHA3 signaling mediates elongation and navigation of axons and trajectories and the assembly of spinal motor neuron axons. In addition, a recent study has suggested that EPHA3/ephrin-A5 signaling limits axon development and governs axon guidance in developing neurons. Also, EPHA3 could modulate cell migration and neurite outgrowth, likely by controlling actin dynamics through CrkII and RhoA signaling. Moreover, increasing evidence suggests that dysregulated EPHA3 signaling is implicated in multiple malignancies with poorer prognosis. Despite these observations, however, little is known about the mechanism contributing to the transcriptional regulation of EPHA3.