Recent studies of a transmembrane form of the prion protein (PrP) have indicated its importance for neuropathogenesis in certain contexts, and have analysed the transacting factors at the endoplasmic reticulum and the mutations within PrP that regulate its appearance. A significant focus for our understanding of the normal role of PrP has emerged from its interaction with copper ions. Studies on two yeast prions have analysed the structure and phenotype of the aggregated conformers underlying the prion state, as well as the interactions regulating their formation and turnover within a dividing cell.