Spinocerebellar ataxia type 7 (SCA7) is unique among CAG/polyglutamine (polyQ) repeat diseases due to dramatic intergenerational instability in repeat length and an associated cone-rod dystrophy retinal degeneration phenotype. SCA7 is caused by a polyQ expansion in the protein ataxin-7. Like other neurodegenerative diseases caused by polyQ expansion mutations, the spectrum of clinical severity and disease progression worsens with increasing polyQ length. Several potential mechanisms for the molecular pathogenesis of polyQ-expanded ataxin-7 have been suggested. These include, but are not limited to, alteration of endogenous ataxin-7 function, abnormal processing and stability of polyQ ataxin-7, and alteration of transcriptional regulation via interaction of polyQ-expanded ataxin-7 with other transcriptional regulators. Ataxin-7's normal function as a transcription factor may contribute to the selective vulnerability of specific cellular populations in SCA7, and the resolution of the mechanistic basis of this pathogenic cascade is a major focus of SCA7 disease research. PolyQ-expanded ataxin-7 can cause non-cell autonomous neurodegeneration in cerebellar Purkinje cells. Advances in understanding SCA7's molecular basis have led to important insights into cell-type specific neurodegeneration. We expect that further study of ataxin-7 normal function, insights into the molecular basis of SCA7 neurodegeneration, and the development of therapeutic interventions for SCA7 will greatly influence related endeavors directed at other CAG/polyQ repeat diseases.