The control of proteolysis in an organism is achieved under normal circumstances through a balance of protease production, degradation and inactivation, via interaction with an endogenous inhibitor. When one of these mechanisms for control of proteolysis fails, it can result in the onset or progression of disease. Control of aberrant proteolysis is, therefore, a potetntial point of therapeutic intervention, and can be achieved either through the replacement of an absent endogenous inhibitor or by dosing with an inhibitor that is specific for a protease that is being over produced. Engineered protein inhibitors of proteases offer the potential to overcome the difficulties involved in identifying specific inhibitors via small-molecule-based approaches.