Enhancing RuvBL1, but particularly RuvBL2 expression, reduces toxic dipeptide repeat proteins in vitro and in vivo models of C9orf72-linked ALS/FTD, suggesting that modulating RuvBL1/2 levels could be a promising therapeutic approach for C9ALS/FTD. Here, RUVBL2 is linked to amyotrophic lateral sclerosis.