Endocytotic pathways ensure that internalized receptor complexes are routed in a highly orchestrated manner to the correct subcellular destinations. This, in turn, determines the consequences of receptor activation through targeting receptors and ligand for recycling or degradation as well as by the formation of signaling complexes within the cell that alter the kinetics and magnitude of activation of specific downstream signal transduction cascades. Thus the control of the fate of activated receptor complexes has profound physiologic and pathophysiologic implications. Rab GTPases, the largest subfamily of the RAS small GTPase superfamily, are the key regulators of endocytosis through decorating and targeting intracellular vesicles and cargoes to appropriate subcellular compartments. The six-fold increase in Rab family members from yeast to man correlates closely with the evolutionary increase in endomembrane complexity compatible with a rapid diversification of function of Rab GTPase decorated vesicles. As the vesicular cargo includes growth factors, nutrients, cytokines, integrins and even pathogens, aberrations in the pathway are likely to exhibit dire consequences. Several genetic diseases driven by mutations in Rab GTPases or their interacting proteins have been identified [1], [2], [3]. Aberrant Rab GTPase function has been implicated in diverse pathophysiologies including loss of hair, skin and eye pigmentation, loss of vision, loss of renal function, mental retardation, muscle skeletal degeneration, immune deficiency, infection, obesity, diabetes and cancer.