Administration of BDA-410, an inhibitor with a relatively higher selectivity for calpain-1 over calpain-2, lowered polyQ-expanded Atx3 cleavage and aggregation, and alleviated neuronal loss and motor symptoms in MJD mice (Li et al., 2007; Simões et al., 2014). Here, CAPN1 is linked to Machado-Joseph disease.