Signalling by ion-channels forms the basis of a great deal of our understanding on how the nervous system functions. In many cases ion-channels activate second messenger pathways which mediate downstream events and in the case of ionotropic receptors much attention has been focussed on the role of the ions themselves in signalling. Recently it has been shown that ion-channels are part of larger multiprotein complexes involving cytoplasmic proteins. I will review data from mice carrying a mutation in Post Synaptic Density 95 (PSD-95) which shows a dramatic change in NMDA receptor signalling when this protein no longer interacts with the NMDA receptor. Multiprotein ion-channel – cytoplasmic protein complexes confer special signalling properties on the ion-channel and may also mediate discrete subcellular localisation. Using the PSD-95 mutant mice as a model we show evidence that disruption of an ion-channel multiprotein complex, without altering expression of the ion-channel itself, alters synaptic plasticity and learning. The ion-channel/receptor multiprotein complex is likely to be a general device for performing the diverse signalling function of receptors.