VCP and amyotrophic lateral sclerosis: Insoluble cytoplasmic TDP-43 aggregates, which are hallmarks of the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) as well as of multisystem proteinopathy (MSP) 1 caused by mutations in the VCP gene encoding p97 (refs. 68–70), were previously reported to be cleared via autophagy19.