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In this review, we highlight current understanding of how this mutation causes disease from research spanning structural biochemistry, cell science, neurobiology, and several model organisms. We now know that homozygosity for \u0394GAG has the same effects as <jats:italic>Tor1a<\/jats:italic><jats:sup>KO<\/jats:sup>, implicating a partial loss of function mechanism in the \u0394GAG\/+\u2009disease state. In addition, torsinA loss specifically affects neurons in mice, even though the gene is broadly expressed, apparently because of differential expression of homologous torsinB. Furthermore, certain neuronal subtypes are more severely affected by torsinA loss. Interestingly, these include striatal cholinergic interneurons that display abnormal responses to dopamine in several <jats:italic>Tor1a<\/jats:italic> animal models. There is also progress on understanding torsinA molecular cell biology. The structural basis of how \u0394GAG inhibits torsinA ATPase activity is defined, although mutant torsinA<jats:sup>\u0394GAG<\/jats:sup> protein also displays some characteristics suggesting it contributes to dystonia by a gain\u2010of\u2010function mechanism. Furthermore, a consistent relationship is emerging between torsin dysfunction and membrane biology, including an evolutionarily conserved regulation of lipid metabolism. Considered together, these findings provide major advances toward understanding the molecular, cellular, and neurobiological pathologies of DYT1\/<jats:italic>TOR1A<\/jats:italic> dystonia that can hopefully be exploited for new approaches to treat this disease. \u00a9 2016 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26880","type":"journal-article","created":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T07:42:36Z","timestamp":1480664556000},"page":"371-381","source":"Crossref","is-referenced-by-count":19,"title":["Membrane defects and genetic redundancy: Are we at a turning point for DYT1 dystonia?"],"prefix":"10.1002","volume":"32","author":[{"given":"Ana","family":"Cascalho","sequence":"first","affiliation":[{"name":"Vlaams Instituut voor Biotechnologie Centre for the Biology of Disease Leuven Belgium"},{"name":"KU Leuven, Department of Human Genetics Leuven 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