To determine whether Stx6 knockout modified the risk of mice developing prion disease, we intracerebrally infected Stx6+/+ and Stx6−/− mice (n = 90/genotype) with a tenfold serial dilution series of 10% (w/v) RML prion-infected brain homogenate and assessed disease development using both clinical and neuropathological diagnoses. Here, STX6 is linked to prion disease.