Serpins are a superfamily of proteins, whose membership is based on the presence of a single common core domain consisting of three β-sheets and 8-9 R-helices, and with a set of highly unusual structural and functional properties that result from the presence of this core domain (Figure 1). Many members are serine proteinase inhibitors, from which the family name derives, with a unique mechanism of action. The initial identification of this superfamily was based on an observation of primary structure similarities between the three proteins human antithrombin, human R1-proteinase inhibitor, and chicken egg white ovalbumin, 1 which clearly established a relationship between these three proteins, despite a sequence identity of only 30% and seemingly very different biological functions, with the first two being inhibitors of serine proteinases and the last an abundant storage protein of egg white without proteinase inhibitory activity. 2 Only with the determi-