Because Sho demonstrated neuroprotective activity against toxicity caused by Dpl and PrP(Δ32–121) in cultured cerebellar granular neurons [1], it was speculated that a loss of Sho levels during prion disease (and any associated neuroprotective activity) in response to PrPSc accumulation may contribute to some of the clinical and/or neuropathological aspects of prion disease. This evidence concerns the gene PRNP and prion disease.