Although various types of stress can activate the JNK pathway, ER stress can trigger neuronal apoptosis through the activation of the inositol-requiring kinase 1 (IRE1)-apoptosis signal regulating kinase 1 (ASK1)-MKK4-JNK signaling pathway in PD and ALS models18. Here, MAP2K4 is linked to amyotrophic lateral sclerosis.