Class E Vps (vacuolar protein sorting) proteins are components of the ESCRTs (endosomal sorting complexes required for transport) which are required for protein sorting at the early endosome. Most of these genes have been identified and genetically characterized in yeast. Recent genetic studies in Drosophila have revealed the phenotypic consequences of loss of vps function in multicellular organisms. In the present paper, we review these studies and discuss a mechanism which may explain how loss of the human Tsg101 (tumour susceptibility gene 101), a vps23 orthologue, causes tumours.