While the involvement of RuvBL1/2 in protein disaggregation and clearance was the initial focus of this study, we present here novel data indicating RuvBL1 and RuvBL2 may assist in reducing the pathogenic DPR proteins found in C9orf72-ALS/FTD by modulating the availability of HRE-containing RNA. Here, C9orf72 is linked to frontotemporal dementia.