Significance Torsin activity critically depends on accessory cofactors that activate their ATPase activity by a poorly understood mechanism. This study establishes the mechanistic framework for Torsin activation, which relies on a complementation of the fragmentary Torsin active site. Given these unusual properties and the fact that Torsin activation is dysregulated in the congenital movement disorder primary dystonia, our results suggest that pharmacological manipulation of Torsin activation may present a novel therapeutic opportunity.