Vacuolar protein sorting-associated protein 4A (VPS4A)

Vacuolar protein sorting-associated protein 4A (VPS4A) is a member of the AAA (ATPases Associated with diverse cellular Activities) family of proteins (UniProt, 2024). It serves as the essential energy-providing component of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery, specifically catalyzing the disassembly and recycling of ESCRT-III polymers from membranes following membrane fission (Vietri et al., 2020). This activity is crucial for various cellular processes, including the formation of multivesicular bodies, the final stage of cytokinesis (abscission), and the budding of enveloped viruses such as HIV-1 and Ebola (NCBI Gene, 2024). Because many viruses rely on VPS4A to exit host cells, it is a significant target for antiviral research. Additionally, VPS4A is implicated in cancer progression and certain rare neurodevelopmental disorders like CIMDAS (Cataracts, intellectual disability, microcephaly, and dermatologic abnormalities syndrome), making it a subject of interest for both oncology and genetic disease research (Rodger et al., 2020). While no clinical drugs currently target VPS4A, its central role in membrane remodeling makes it a high-priority candidate for the development of novel therapeutic inhibitors.

Other names

VPS4SKD1SKD1AVacuolar protein sorting 4 homolog AProtein SKD1

Inhibition of ATPase activity prevents the disassembly of ESCRT-III complexes, thereby blocking membrane fission processes such as viral budding and cytokinesis.