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Animal and <jats:italic>in vitro<\/jats:italic> models have revealed \u03b2\u2010III spectrin, a cytoskeletal protein present throughout the soma and dendritic tree of cerebellar Purkinje cells, to be required for the maintenance of dendritic architecture and for the trafficking and\/or stabilisation of several membrane proteins: ankyrin\u2010R, cell adhesion molecules, metabotropic glutamate receptor\u20101 (mGluR1), voltage\u2010gated sodium channels (Na<jats:sub>v<\/jats:sub>) and glutamate transporters. This scaffold of interactions connects \u03b2\u2010III spectrin to a wide variety of proteins implicated in the pathology of many SCAs. Heterozygous mutations in the gene encoding \u03b2\u2010III spectrin (<jats:italic>SPTBN2<\/jats:italic>) underlie SCA type\u20105 whereas homozygous mutations cause spectrin associated autosomal recessive ataxia type\u20101 (SPARCA1), an infantile form of ataxia with cognitive impairment. Loss\u2010of \u03b2\u2010III spectrin function appears to underpin cerebellar dysfunction and degeneration in both diseases resulting in thinner dendrites, excessive dendritic protrusion with loss of planarity, reduced resurgent sodium currents and abnormal glutamatergic neurotransmission. The initial physiological consequences are a decrease in spontaneous activity and excessive excitation, likely to be offsetting each other, but eventually hyperexcitability gives rise to dark cell degeneration and reduced cerebellar output. Similar molecular mechanisms have been implicated for SCA1, 2, 3, 7, 13, 14, 19, 22, 27 and 28, highlighting alterations to intrinsic Purkinje cell activity, dendritic architecture and glutamatergic transmission as possible common mechanisms downstream of various loss\u2010of\u2010function primary genetic defects. A key question for future research is whether similar mechanisms underlie progressive cerebellar decline in normal ageing.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp7081-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp271195","type":"journal-article","created":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T16:26:53Z","timestamp":1453998413000},"page":"4661-4676","source":"Crossref","is-referenced-by-count":27,"title":["Cerebellar ataxias: \u03b2\u2010III spectrin's interactions suggest common pathogenic pathways"],"prefix":"10.1113","volume":"594","author":[{"given":"Emma","family":"Perkins","sequence":"first","affiliation":[{"name":"Centre for Integrative Physiology University of Edinburgh  Hugh Robson Building, George 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