In superoxide dismutase 1 (SOD1)-associated ALS, the mutant SOD1 protein is misfolded and forms aggregates, which trigger the unfolded protein response and endoplasmic reticulum stress, leading to PERK and PKR-mediated ISRs (Lindberg et al, 2005; Nishitoh et al, 2008; Saxena et al, 2009; Sun et al, 2015b). Here, SOD1 is linked to amyotrophic lateral sclerosis.