While in a 'Methods' series, this is not a recipe book, rather a collection of discussions on the prion protein's role in normal and infected animals. The association between the protein's abnormal conformation and pathology is now widely accepted, but how it 'replicates' and spreads to the brain to kill neurones in strain-specific ways is still largely a mystery. The book presents the protein as a binder of copper, protector of cells, neurotoxin, and agent of precise neuronal targeting. Several chapters explore the use of disease models in normal and transgenic mice, tissue slices and mammalian and yeast cell cultures to examine the role of the prion protein and its mutations in disease. This is no introductory textbook to the prion protein; some knowledge of prions is required to appreciate the relevance of the varied contents and to place them within the context of TSE molecular pathology.