UPR and CHOP induced prior to symptom onset in SOD1G93A mouse models (Atkin et al., 2006; Kikuchi et al., 2006; Saxena et al., 2009).PERK, IRE1 and ATF6 upregulated in post-mortem human spinal cord tissues (Atkin et al., 2008).Deletion of BIM, XBP-1, ASK1, Puma or ATF4 delays disease onset or extends survival in ALS mouse models (Kieran et al., 2007; Nishitoh et al., 2008; Hetz et al., 2009; Matus et al., 2013a,b).Pharmacological inhibition of eIF2α dephosphorylation extends survival of ALS mouse models (Boyce et al., 2005; Saxena et al., 2009). This evidence concerns the gene ERN1 and amyotrophic lateral sclerosis.