The changing landscape in translocator protein (TSPO) function

• Recent data question the role of TSPO in steroidogenesis and the MPT and suggest that TSPO is not involved.
• Exploiting TSPO upregulation in pathologies for diagnostic imaging has the potential to grow and extend across multiple fields.
• The physiological function of TSPO remains undefined and its future as a therapeutic target needs to be carefully re-evaluated.

Translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is an outer mitochondrial membrane protein. TSPO has been shown to cooperate with steroidogenic acute regulatory protein (StAR) and function in the transport of cholesterol into mitochondria. TSPO has also been considered as a structural component of the mitochondrial permeability transition pore (MPTP). However, recent advances have changed these views of TSPO's functions and have prompted a re-evaluation of established concepts. This review summarizes the history of TSPO, key elements of the debate, and functional experiments that have changed our understanding. Moving forward, we examine how this fundamental change impacts our understanding of TSPO and affects the future of TSPO as a therapeutic and diagnostic target.