Work performed in animal models of frontotemporal dementia, Parkinson’s disease, Huntington’s disease, and spinocerebellar ataxia type 3 has shown that calpain-mediated fragmentation of the proteins implicated in disease (TDP-43, α-synuclein, huntingtin, and ataxin-3) either increases their tendency to aggregate or directly leads to neurotoxicity82–85. This evidence concerns the gene ATXN3 and frontotemporal dementia.