ERBB4 and amyotrophic lateral sclerosis: The reason for NRG1 upregulation is unclear; we postulate that upregulation of the NRG1 ligand may occur as a feedback loop in response to reduced ERBB4/HER4/ALS19 signaling caused by loss-of-function ERBB4/HER4/ALS19 mutations or dampened ERBB4/HER4/ALS19 expression that occurs for other reasons in ALS [9, 11, 37].