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. This evidence concerns the gene PRND and prion disease.