Endocytosis is a versatile tool to regulate the intensity, localization, half-life and function of signaling complexes (signalosomes) that form in cells upon binding of growth factors, cytokines and morphogens to their cognate receptors. Endocytic adaptors are non-catalytic proteins that assemble effectors and structural components of the endocytic machinery around the trafficking cargo and serve as scaffolds for signalosomes, which in turn modify their location and activity by various post-translational modifications. We discuss how breakdowns in the function of endocytic adaptors might facilitate impairment of tissue homeostasis and consequent tumor development.