Given that VCP is reported to possess unfoldase activity mediated by its ATPase function [90] and that protein aggregation, frequently observed in ALS patient motor neurons, is thought to be driven by unstructured regions susceptible to unfolding [91], we hypothesized that cyclin F mutants, which activate VCP’s ATPase activity, lead to excessive unfoldase activity of VCP, resulting in abnormal protein unfolding and subsequent aggregation. Here, DNAH8 is linked to amyotrophic lateral sclerosis.