VPS4B (vacuolar protein sorting 4 homolog B) is an AAA-ATPase that functions as a critical component of the ESCRT (endosomal sorting complex required for transport) machinery, primarily responsible for disassembling ESCRT-III complexes through ATP hydrolysis 1. The protein plays essential roles in multiple membrane remodeling processes, including exosome biogenesis, cytokinesis abscission, and autophagy regulation. VPS4B modulates exosome secretion, with its depletion actually increasing EV-associated protein secretion 1. In cancer biology, VPS4B demonstrates dual functions: it promotes autophagic cell death in breast cancer through ESCRT-III assembly with CHMP2B 2, while its overexpression in hepatocellular carcinoma correlates with poor prognosis and accelerated cell proliferation 3. VPS4B also orchestrates nuclear envelope stress responses by regulating ESCRT-III dynamics, with insufficient expression leading to inadequate stress responses and DNA damage 4. Additionally, the protein facilitates lipid droplet transfer from adipocytes to cancer cells through O-GlcNAc modification-dependent mechanisms 5. Unlike VPS4A, VPS4B appears to have a more canonical role in membrane remodeling processes 6, making it a potential therapeutic target across various diseases 7.