EPHA4 and amyotrophic lateral sclerosis: While other agents are also being developed to manipulate binding of ephrins with EphA4 for ALS therapeutics (Qin et al., 2015; Schoonaert et al., 2017), our results suggest that directly targeting ephrinB2 is a promising strategy to modulate both Eph-ephrin signaling and astrocyte-MN interactions in ALS.