On the cover, adenylyl cyclases that are regulated by Ca²⁺ are regulated exclusively by capacitative Ca²⁺-entry, i.e. the entry of Ca²⁺ that is triggered by depletion of intracellular stores; elevation of cytosolic Ca²⁺ by ionophore-mediated entry, or release from intracellular stores, is ineffective. In this issue Smith et al., pages 6025-6031 (6025), explore the need for the localization of adenylyl cyclases in caveolae or rafts (indicated in green) to ensure this regulation.