AbstractThe extracellular signal‐regulated kinase cascade is a central signaling pathway that is stimulated by various extracellular stimuli. The signals of these stimuli are then transferred by the cascade's components to a large number of targets at distinct subcellular compartments, which in turn induce and regulate a large number of cellular processes. To achieve these functions, the cascade exhibits versatile and dynamic subcellular distribution that allows proper temporal and spatial modulation of the appropriate processes. In this review, we discuss the intracellular localizations of different components of the ERK cascade, and the impact of these localizations on their activation and specificity. © 2009 International Union of Biochemistry and Molecular Biology, Inc.