ATXN8 (ataxin 8) is located on chromosome 13 and is part of a bidirectional transcription unit with ATXN8OS, where pathogenic expansions of CTA/CTG repeats cause spinocerebellar ataxia type 8 (SCA8) 1. The gene exhibits complex pathogenesis with bidirectional expression of both CUG (ATXN8OS) and CAG (ATXN8) expansion transcripts 1. ATXN8 expression is modulated by a functional -62 G/A promoter polymorphism, with the -62G allele showing significantly higher transcriptional activity than the -62A allele 12. The transcription factor CCAAT/enhancer-binding protein alpha binds to the ATXN8 proximal promoter to upregulate expression 2. SCA8 demonstrates highly variable penetrance and clinical pleiotropy, with expanded alleles found not only in cerebellar ataxia but also associated with amyotrophic lateral sclerosis, frontotemporal dementia, and atypical parkinsonism 31. The disease shows genetic synergism with STUB1 mutations, which may modify disease expression 4. In cellular models, ATXN8 large alleles increase cell death and caspase 3 activity when exposed to cellular stress, and show significantly higher expression levels compared to normal alleles 1. The repeat expansions are prone to dynamic mutations during intergenerational inheritance 5.