Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph Disease, is a rare neurodegenerative condition arising from a mutation in the ATXN3 gene. This genetic alteration leads to an expanded CAG triplet, which encodes an abnormally long polyglutamine (polyQ) tract within the ubiquitous protein Ataxin-3. As a deubiquitinating enzyme (DUB), Ataxin-3 plays a vital role in cellular protein quality control; however, its tendency to form aggregates remains a focal, yet highly debated, subject in scientific literature. At the heart of this process lies the N-terminal Josephin Domain (JD). This unit contains the catalytic site and features a remarkably flexible hairpin region, which is thought to modulate protein behavior, influencing both ubiquitin recognition and the exposure of amyloidogenic surfaces.