The well-conserved transmembrane translocator proteins (TSPOs) were first identified as peripheral benzodiazepine receptors, owing to their affinity for Valium. In eukaryotes, TSPOs have been implicated in transporting cholesterol across the mitochondrial membrane for steroid biosynthesis, although this function has been disputed by recent studies showing that TSPO-knockout mice are not steroid defective. TSPOs also bind to porphyrins, including heme and its precursor PpIX, and a bacterial TSPO was recently shown to catalyze the photo-oxidative enzymatic degradation of PpIX. Despite their presence across all kingdoms of life and their involvement in human pathologies from cancer to cardiovascular diseases and neurological disorders, TSPOs' mechanism and physiological roles remain unclear. Two groups have now independently reported crystal structures of bacterial TSPOs, providing important clues to decipher the confounding functions of these proteins. Hendrickson and colleagues solved structures of Bacillus cereus TSPO in monomeric and dimeric forms and provided atomic details of the binding to the benzodiazepine-like drug PK-11195. Ferguson-Miller and colleagues reported structures of Rhodobacter sphaeroides TSPO—all showing the protein as dimer—including a porphyrin-bound form and a mutant mimicking a disease-associated polymorphism. All crystal structures showed substantial similarity, with each protomer comprising five transmembrane helices, and were similar to a previous NMR structure of mouse TSPO, which, however, displayed distinct relative positions and orientations of some helices. Ferguson-Miller and colleagues showed that mutations analogous to the human disease–associated A147T polymorphism decrease binding to cholesterol and porphyrin, and Hendrickson and colleagues demonstrated that these mutants are unable to catalyze PpIX degradation. What about function? Interestingly, the dimer interface seen in the crystal structures is too tight for a transport pathway, but Ferguson-Miller and colleagues observed several monoolein molecules bound to protein-surface grooves; this led them to suggest that transport of cholesterol might occur along the external surface of TSPO, possibly with the involvement of other proteins. In addition, biochemical analyses by Hendrickson and colleagues showed that enzymatic degradation of PpIX to a new heme derivative, bilindigin, is a general feature of TSPOs, thus suggesting that the protein might protect cells against oxidative stress. Although many questions remain, these new structures provide a basis to elucidate TSPOs' mechanism and physiological roles. (Science 347, 551–555, 2015 and Science 347, 555–558, 2015)