The Wnt signalling cascade is an ancient cell communication system that operates in all animals and humans to control embryonic development and stem cells in adult tissues. If dysregulated, it is also one of the main cancer drivers, most notably in the bowel. Transduction of the Wnt signal from the cell membrane to the nucleus relies on the signalosome, a dynamic but poorly defined multi-protein complex that is assembled at the cytoplasmic face of the receptor complex following its binding to the Wnt signal. Gammons and colleagues have purified the core components of the Wnt signalosome and used a combination of biophysical and genome-engineering techniques to determine how the Axin scaffold and its GSK3 kinase effector bind to the LRP6 co-receptor. Their work provides insights into how these interactions initiate Wnt signal transduction by promoting signalosome assembly at the cytoplasmic tail of LRP6 and how they terminate signalling by promoting its detachment from LRP6. These authors also discovered that signalosome assembly relies on the AP2 clathrin adaptor which must bind to LRP6 to promote efficient signal transduction. This discovery led them to propose a model according to which the Wnt-driven clustering of LRP6 within clathrin-coated locales allows the signalosome to dock at adjacent LRP6 receptor tails through its Axin-GSK3 core complex while also exposing the signalosome to kinases that are co-targeted by AP2 to these locales to modulate its activity in Wnt signal transduction.