VPS4A and hereditary spastic paraplegia: More generally, our quantitative definition of the ESCRT-III-MIT interactome should provide a basis for probing how disruption of ESCRT-III and MIT cofactor activities can contribute to disease states such as hereditary spastic paraplegia (Ciccarelli et al., 2003), or can be used therapeutically, for example in anti-cancer strategies based on VPS4 synthetic lethality (Neggers et al., 2020; Szymańska et al., 2020).