Significance Torsins belong to the AAA+ (ATPases associated with a variety of cellular activities) ATPase superfamily, the members of which disassemble protein complexes or unfold proteins. Here, we provide evidence that the activity of Torsins is tightly regulated by two proteins that reside in the endoplasmic reticulum and the perinuclear space. This regulatory mechanism provides the framework for a better understanding of phenotypes in animal models, and allows us to define the molecular defect underlying TorsinA dystonia.