We have previously demonstrated that the small GTPase Rab5 is a master regulator of early endosome biogenesis. Using an in vitro reconstitution system, we could show that the Rab5 machinery is essential for efficient membrane fusion, as SNAREs alone fuse membranes very poorly. Silencing of Rab5 in the mouse liver in vivo causes a severe loss of the entire endo-lysosomal pathway, suggesting that it is essential for endocytosis and assembly of the machinery that confers structural and functional identity to early endosomes. We are currently dissecting the molecular mechanisms whereby the Rab5 effectors mediate endosomal membrane tethering and fusion using a combination of protein structure, biochemical and biophysical approaches. Furthermore, we have found that the endosome tethering and fusion machinery responds to tyrosine kinase receptors to regulate their packaging in endosomes and determine the amplitude, lifetime and robustness of the signalling response.