More than one third of the drugs used today act at G protein-coupled receptors (GPCRs). GPCRs and their downstream signalling cascades are the basis for current pharmacotherapeutic concepts. More drugs interfere with GPCRs than with any other protein or cell structure. New insights into previously largely unknown non-canonical regulatory mechanisms of G-protein signalling pathways open up new approaches for promising pharmacotherapeutic interventions. Non-canonical G-protein signalling in particular is predicted to have great potential for precision medicine. Our RTG aims to uncover the underlying mechanisms, functions and consequences of non-canonical G protein signaling and to develop novel therapies.