Serpins constitute a superfamily of proteins that possess a unique tertiary structure and mechanism of proteinase inhibition. In humans, serpins constitute 10% of the plasma proteins and are best known as critical regulators of both the thrombotic and fibrinolytic systems. Serpins also participate in the regulation of the complement cascade, angiogensis, tumor metastasis, apoptosis and innate immunity. Considering the importance of these molecules in regulating proteolytic cascades, it is not surprising to find that this loss-and gain-of function mutations result in significant human...