The present invention provides nucleic acids encoding the Doppel ("Dpl") protein, Dpl peptides, and assays utilizing the Dpl nucleic acids and/or peptides. In related aspects the invention features expression vectors and host cells comprising nucleic acids that encode a human Dpl polypeptide. The present invention also relates to antibodies that bind specifically to a human Dpl polypeptide, methods for producing human Dpl polypeptides, methods for identifying cells expressing Dpl, methods for using the Dpl gene and the Dpl polypeptide to alter cellular function and prion infectivity in culture or in vivo, and identification of individuals at risk for prion disorders by detecting alteration in Dpl coding and regulatory sequences and Dpl expression levels.