Ataxin-2, the gene product of the human spinocerebellar ataxia type 2 (SCA2/ATXN2) gene, is a basic protein with two domains (Sm1 and Sm2) implicated in RNA splicing and protein interaction. Ataxin-2 interacts with a putative RNA-binding protein ataxin-2-binding-protein 1 (A2BP1), which is expressed in muscle and brain. Ataxin-2 is ubiquitously expressed with highest levels in the cytoplasm of Purkinje cells. Both A2BP1 and ataxin-2 are localized to the trans-Golgi network. Mice expressing ataxin-2 with polyglutamine show progressive functional deficits accompanied by loss of Purkinje cell dendritic arbor and eventually loss of Purkinje cells. In conclusion, expansion of ataxin-2 results in spinocerebellar ataxia type 2, which affects the cerebellum and other areas of the central nervous system.