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Doppel is a paralog of the normal prion protein, PrP C . It has been suggested that Doppel can compensate for the absence of PrP C in PrP 0=0 mice. In this work, we tested whether Doppel and PrP C share the same cell location, thereby sharing the same neighboring cell components, probably required to share the same cell function. Our results show that, at detergent conditions in which membrane rafts were intact, neither PrP C and Doppel co-immunoprecipitate with the appropriate antibodies, nor was Doppel retained by a Cu 2+ IMAC resin, as PrP C does. This indicates that, although Doppel is a raft-associated protein as is PrP C , both proteins are not present in the same membrane microenvironment, and they probably do not perform the same function. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.