Lipid membrane can enhance prion protein (PrP) pathological fibrillogenesis.A neuronal paralog of PrP, namedShadoo (Sho), is localized to similar membrane environment as PrPand can also convert to amyloid-like fibrilles.To gain insight into the role of Shoin prion diseases, we studied Sho interactionswith cellular membrane models. Showas found to bind anionic lipid vesicles. Spectroscopic and microscopic data showed that membrane-associated Sho slowly converted into amyloid fibers. Furthermore, binding of Sho to anionic liposomes has a disruptive effect on the integrity of the lipid bilayer leading to the formation ofsupramolecular lipid-protein complexes. In consequence, therole of Sho in prion diseases might depend on the oligomerzation state of Shobut also the nature of theselipoproteinassembles.