The cellular prion protein (PrPC) is found prominently at the synapse. However, its role at the nerve termini and elsewhere is unknown. Here we discuss research presented at the 2005 International Institute for Complex Adaptive Matter (I2CAM) first Annual Amyloid Conference that provides insight into the role of synaptic PrPC. The prion protein can interact and facilitate copper uptake at the synapse, is presumed to oligodimerize to facilitate putative cell-cell adhesion, and it transports toward the synapse by fast microtubule-based anterograde transport. While PrPC appears to be involved in all these processes, the mechanisms of PrPC function in each of them remain unclear. A role for PrPC in these distinct processes suggests a complex role for this protein at the synapse. Unraveling PrPC function will likely entail employing combined approaches that take into account its possible multifaceted functions.