VPS11 is a core subunit of the CORVET and HOPS endosomal tethering complexes that mediates vesicle-mediated protein trafficking to lysosomal compartments 12345. VPS11 functions as a Rab5 effector in early endosome fusion and is recruited to Rab7-positive late endosomes to regulate late endocytic, phagocytic, and autophagic traffic toward lysosomes 12345. It is required for fusion of endosomes and autophagosomes with lysosomes and for the transition from early to late endosomes 56. Beyond its canonical membrane trafficking role, VPS11 acts as an E3 ubiquitin ligase that fine-tunes signaling pathways including Wnt, estrogen receptor α, and NFκB 7. VPS11 dysfunction causes Dystonia 32 and hypomyelinating leukodystrophy 12, characterized by neurological deficits including progressive visual and sensorimotor abnormalities 8. Clinically, VPS11 dysregulation impairs autophagosome-lysosome fusion, contributing to hepatic lipid deposition in non-alcoholic fatty liver disease 9. Additionally, VPS11 regulates PD-L1 trafficking and stability, with VPS11 inhibition enhancing immunotherapy efficacy against tumors 10. Pathogenic viruses exploit VPS11 function; tick-borne encephalitis virus protein prM binds VPS11 to constrain autolysosome formation 11.