The relevance of this EAAT2-derived signaling mechanism was demonstrated in vivo, in a mutant SOD1 mouse model of amyotrophic lateral sclerosis (ALS), where knock-in of a modified Slc1a2 isoform with a defective caspase-3 cleavage site prolonged the life span of mice afflicted by the disease (Rosenblum et al., 2017). Here, SOD1 is linked to amyotrophic lateral sclerosis.