Previously, Tsuda and colleagues reported that a protein called amyotrophic lateral sclerosis 8 (ALS8) known to be associated with the pathogenesis of ALS is cleaved and then secreted to bind directly to the EphA4 ectodomain;65 however, it is not yet clear whether ALS8 activates downstream signaling of EphA4. The gene discussed is EPHA4; the disease is amyotrophic lateral sclerosis.