G-protein-mediated signalling processes are involved in sweet and bitter taste transduction. In particular, the G protein α-subunit gustducin has been implicated in these processes. One of the limiting factors for the time-course of cellular responses induced by tastants is therefore the intrinsic GTPase activity of α-gustducin, which determines the lifetime of the active G protein complex. In several signalling systems specific ‘regulator of G protein signalling’ (RGS) proteins accelerate the GTPase activity of G protein α-subunits. Using differential screening approaches, we have identified a novel RGS protein termed RGS21, which represents the smallest known member of this protein family. Reverse transcription polymerase chain reaction and in situ hybridization experiments demonstrated that RGS21 is expressed selectively in taste tissue where it is found in a subpopulation of sensory cells. Furthermore, it is coexpressed in individual taste cells with bitter and sweet transduction components including α-gustducin, phospholipase Cβ2, T1R2/T1R3 sweet taste receptors and T2R bitter taste receptors. In vitro binding assays demonstrate that RGS21 binds α-gustducin in a conformation-dependent manner and has the potential to interact with the same Gα subtypes as T1R receptors. These results suggest that RGS21 could play a regulatory role in bitter as well as sweet taste transduction processes.