Though the OR region comprises the main Cu-binding region of PrPC, accommodating up to 4 Cu (II) ions per polypeptide chain, a direct causative link between copper and prion disease was challenged by the observation that transgenic mice completely lacking the OR region (PrPΔ32–93) were still susceptible to infection with laboratory prion isolates [6]. Here, PRNP is linked to prion disease.