Mice lacking the E3 ubiquitin ligase, mahogunin ring finger-1 (MGRN1) or the type I transmembrane protein, attractin (ATRN) develop age-dependent CNS vacuolation that is histologically similar to that associated with prion diseases, without the accumulation of protease-resistant PrPSc[3], [4]. Here, MGRN1 is linked to prion disease.