A prion protein (PrP)-like protein, Doppel (Dpl) is a homologue of cellular PrP (PrPC). Immunoblotting revealed heterogeneous glycosylation patterns of Dpl and PrPC in several cell lines and tissues, including brain and testis. To investigate whether the glycosylation and modification of Dpl and PrPc could influence each other, PrP gene (Prnp)-deficient neuronal cells, transfected with Prop and/or the Dpl gene (Prnd), were analyzed by deglycosylation with peptide N-glycosidase F. The modification of Dpl was not influenced by PrPC, whereas an N-terminally truncated fragment of PrPC was reduced by Dpl expression. These results indicated that Dpl was glycosylated in a cell type- and tissue-specific manner regardless of PrPC, while PrPC endoproteolysis was modulated by Dpl expression. (C) 2010 Elsevier Inc. All rights reserved.