Discovering the biological roles of a protein is best accom-plished by observing the consequences of its removal. However, such loss-of-function studies are rarely straightforward. In the case of genetic experiments, including those dealing with knockout mice, gene functions in one tissue type are often disguised by deleterious phenotypes, including lethality, in another. Even when this problem is overcome, for example, by tissue-specific gene deletion using the Cre/loxP system, it can be difficult to dissect primary from secondary effects to determine the molecular basis of a phenotype. The difficulty lies in the speed at which the biological events being studied occur. For example, after transcription of the Cre recombinase is induced, considerable time will lapse before recombination of the targeted gene and dissipation of preexisting pools of the target gene’s RNA and protein. During this period, the studied cells could have, for example, responded to extracellular signals, undergone cell divisions, changed position or shape, and even differentiated into a new cell type. Alternative methods, such as RNA interference or smallmolecule inhibition, allow regulation of the protein of interest during tighter time windows. Unfortunately, these techniques have their own shortcomings. RNA interference suffers from nonspecific effects, unpredictable degrees of ‘‘knockdown,’’and slow kinetics of onset and reversibility. Small-molecule regulation is generally very fast and usually reversible; however, identifying or developing a small molecule that is genuinely specific with reliable pharmacokinetics challenges even the largest pharmaceutical company. To this end, researchers have devoted considerable energy to develop new technologies that merge gene-based methods (to create impeccable specificity) with chemicalbased strategies (to provide rapid on/off regulation). In a recent issue of PNAS, Pratt et al.(1) report a new approach that uses a generic drug to induce the recovery of a native target protein from a fusion protein that is otherwise destined for destruction (1). This method adds to the growing toolbox available to researchers interested in perturbing biological systems closer to physiologically relevant speeds. Much of biology is regulated at the molecular level by changes in the proximity of molecules. For example, receptor dimerization is a common way that signals are transduced from the membrane into the cell. Similarly, protein phosphorylation requires recruitment of the substrate to its kinase, and transcriptional regulation depends on cooperative interactions between multiple transcription factors. Coopting this universal aspect of biological regulation by artificially inducing dimerization is an effective way to regulate and study cellular events (2). Small molecules that are able to simultaneously bind to two protein domains can be used for just this purpose. These protein domains can be individually fused to different proteins or protein moieties so that addition of the compound induces the association of the protein domains and triggers molecular responses, including receptor activation (2), nucleocytoplasmic transport (3), transcriptional activation (4), and the timing of mitotic chromosome separation (5). Although the original molecules were homodimerizers made by joining two molecules of FK506, one commonly used tripartite complex is the FKBP12–rapamycin–FRB system. Rapamycin is a macrolide antibiotic that is approved for pharmaceutical use as an immunosuppressant and shows considerable promise as an antitumor agent. Its suitability as a drug is based on its ability to inhibit mTor, a protein kinase that is involved in cell growth and proliferation …