During the generation of a knockout line of mice we noted an early movement disorder that was inherited independently of targeting vector transmission. We embarked on a series of experiments to identify the genetic lesion underlying this movement disorder and to identify a cognate disease and corresponding mutation in humans. Here we describe this effort and the discovery of deletion at the ITPR1 locus as a cause of this disorder in mice and of spinocerebellar ataxia 15 (SCA15) in humans.