While antisense oligonucleotide (Ling et al., 2018) or ubiquitous genetic knockdown (Rué et al., 2019b) of EphA4 in ALS mouse models does not affect disease phenotype, inhibition of EphA4 signaling using EphA4-Fc partially preserves motor function and MN-specific genetic knockdown delays symptomatic onset and protect MNs in ALS mice (Zhao et al., 2018). The gene discussed is EPHA4; the disease is amyotrophic lateral sclerosis.