EPHB2 and amyotrophic lateral sclerosis: EphB’s are centrally involved in regulating subcellular localization of ionotropic glutamate receptor subunits to excitatory synapses (Hanamura et al., 2017; Nolt et al., 2011), raising the intriguing possibility that enhanced ephrinB2-EphB2 signaling results in increased glutamate receptor activation in MNs and consequently may be contributing to excitotoxicity that plays a well-known role in ALS.