While the exact function of the cellular prion protein (PrP(C)) remains unknown, there are several leads due to increasing knowledge on the localisation and interaction of PrP(C) with other molecules. This chapter will concentrate on these aspects. Identified ligands of PrP(C) mainly belong to the categories of heat-shock proteins, membrane-bound receptors, or heparan sulphates. The possible synaptic role of PrP(C) has been exemplified by electrophysiological findings in PrP(o/o) mice and the studies of PrP(C) as a copper-binding molecule that could regulate the copper content of the synaptic cleft. The latter property of PrP(C) may also endow PrP(C) with the activity of a copper-dependent superoxide dismutase. Binding of PrP(C) to signalling molecules suggests a role as a transmitter of information from the extracellular milieu to the cell and a trigger for a molecular cascade. This agrees with new data on PrP(C) receptors and the role of PrP(C) in cell survival.