Intracellular α2C-Adrenoceptors: Storage depot, stunted development or signaling domain?

► We review the dilemma of GPCRs with a predominant intracellular localization. ► The major focus is on α2C-Adrenoceptors. ► GPCRs can be preferentially retained during biosynthesis in the ER and Golgi. ► Retention can reflect incomplete processing or targeted protein interactions. ► Appropriate stimuli can mobilize GPCRs to the surface or activate them in situ.