PERK signaling was shown to have a primary role in amyotrophic lateral sclerosis (ALS) using the SOD1 transgenic mouse model after targeting the pathway with different pharmacological or DNA-modifying approaches, leading, according to the experimental conditions, to an aggravation (enhanced SOD1 aggregation) or an amelioration (extended life span) of the ALS phenotype [66]. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.