PRNP and prion disease: Proteins encoded by genetic loci that modify susceptibility to, or incubation time in, prion disease might do so by involvement with the normal functional pathways of PrP, either as a ligand or homologue, and several putative PrP ligands have been proposed.16 The recently characterised prion protein family,, 17 including Doppel18 and Shadoo,19 are pre-eminent candidate functional homologues of PrP, but several lines of evidence contradict involvement of PRND genetic variation and Dpl in human prion disease.17, 20, 21