Mutations in multiple other genes encoding proteins that are broadly involved in protein quality control pathways (e.g., C9ORF72, VCP, UBQLN2), RNA metabolism (e.g., TARDBP, FUS, MATR3), and cytoskeletal homeostasis (e.g., NEK1, TUBA4A, PFN1), cause ALS that is phenotypically indistinguishable from mutSOD1-driven disease.28,29 How mutations in proteins with unrelated functions converge to cause the selective death of MNs in patients is an outstanding question. Here, MATR3 is linked to amyotrophic lateral sclerosis.