Mounting evidence suggests that the UPRmt is activated in the context of ALS/FTD-related mutant TDP-43, SOD1, CHCHD10, and FUS; however, it remains unclear what role this UPRmt activation plays in the ALS/FTD pathobiology (Riar et al., 2017; Deng et al., 2018; Anderson et al., 2019; Pharaoh et al., 2019; Wang et al., 2019; Straub et al., 2021). This evidence concerns the gene SOD1 and amyotrophic lateral sclerosis.