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To evaluate the role of <jats:italic>VPS13D<\/jats:italic> mutations, we evaluated a <jats:italic>Drosophila<\/jats:italic> knockout model and investigated mitochondrial function in patient\u2010derived fibroblast cultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exome sequencing identified compound heterozygous mutations in <jats:italic>VPS13D<\/jats:italic> on chromosome 1p36 in all 7 families. This included a large family with 5 affected siblings with spinocerebellar ataxia with saccadic intrusions (<jats:italic>SCASI<\/jats:italic>), or spinocerebellar ataxia, recessive, type 4 (<jats:italic>SCAR4<\/jats:italic>). Linkage to chromosome 1p36 was found in this family with a logarithm of odds score of 3.1. The phenotypic spectrum in our 12 patients was broad. Although most presented with ataxia, additional or predominant spasticity was present in 5 patients. Disease onset ranged from infancy to 39 years, and symptoms were slowly progressive and included loss of independent ambulation in 5. All but 2 patients carried a loss\u2010of\u2010function (nonsense or splice site) mutation on one and a missense mutation on the other allele. Knockdown or removal of <jats:italic>Vps13D<\/jats:italic> in <jats:italic>Drosophila<\/jats:italic> neurons led to changes in mitochondrial morphology and impairment in mitochondrial distribution along axons. Patient fibroblasts showed altered morphology and functionality including reduced energy production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our study demonstrates that compound heterozygous mutations in <jats:italic>VPS13D<\/jats:italic> cause movement disorders along the ataxia\u2013spasticity spectrum, making <jats:italic>VPS13D<\/jats:italic> the fourth VPS13 paralog involved in neurological disorders. 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