Further analysis of MJD patient-derived fibroblasts and MJD animal models delivered additional proof of a pathological calpain overactivation, which caused subsequent proteolytic perturbations in neuronal substrate proteins and might be linked to a described dysregulation of calcium homeostasis by polyQ-expanded Atx3 (Chen et al., 2008; Simões et al., 2012; Weber et al., 2020). Here, ATXN3 is linked to Machado-Joseph disease.