Interestingly, two treatment studies using calpain inhibitor calpeptin and BLD-2736, a novel inhibitor of calpain-1, -2, and -9, in MJD zebrafish, did not primarily link the observed beneficial effects on Atx3 aggregation and motor phenotype with a reduced fragmentation of Atx3, but with its higher turnover via the autophagic system (Watchon et al., 2017; Robinson et al., 2021), which is known to be modulated by calpain activity (Weber et al., 2019a). This evidence concerns the gene CAPN1 and Machado-Joseph disease.