The most intuitive way of thinking about spatial redistribution of entropy is through portions of a protein acting as 'entropic reservoirs' that are poised to greatly change their conformational ensemble upon perturbation. Intrinsically disordered regions (IDRs) are prime candidates to serve as these entropic reservoirs. In human UDP-α-D-glucose-6-dehydrogenase (UGDH), the deletion of the Cterminal tail IDR reduces the affinity for the allosteric metabolite UDP-xylose by ~10-fold, despite making no direct contact with the ligand . The ligand-bound state stabilizes altered contacts near the IDR, which allows the IDR to adopt an even more expanded conformational ensemble relative to the apo state. Thus, a major driving force for binding is increased disorder and entropy in an already high-entropy IDR. To test this model, they showed that binding affinity lacked sequence dependence in the IDR region, but that the length of the IDR was strongly predictive of affinity. These results are consistent with an entropic force mode where the IDR can impact the globular protein region, and this impact is determined not only by the length of the IDR, but also by the underlying conformational ensemble of the IDR . A similar interplay likely modulates allostery in the hTS example discussed above. In hTS, the interaction between an N-terminal IDR and the globular domains may influence the side chain dynamics underlying positive cooperativity. Intriguingly, this IDR segment is absent in the E coli homolog of TS, which is also dimeric but is non-cooperative . In addition to IDRs, local unfolding provides another potential "entropic reservoir". In adenylate kinase, mutations that affect the local unfolding of lid subdomains are important for different aspects of catalysis, with an underlying entropic mechanism driving the changes in free energy . These examples suggest that the modulation of thermodynamics by the entropy of unfolded or intrinsically disordered segments influences the dynamics of folded regions and can, therefore, tune the free energy of binding and allostery.