Mutant SOD1 (mSOD1) leads to ALS pathogenicity by causing ER stress and especially by activating the PERK pathway through several mechanisms [92]: (1) mSOD1 interferes with COPII vesicular transport [93], (2) mSOD1 showed interaction with Derlin1, an ER membrane protein involved in ERAD, which impaired the ERAD pathway in ALS models [63,64,94], (3) accumulation of mutant SOD1 was reported in the ER lumen, where it binds BiP, inducing ER-stress. This evidence concerns the gene EIF2AK3 and amyotrophic lateral sclerosis.