Hereditary angioedema C1 inhibitor (C1-INH) not only inhibits C1r, C1s, and MASP2 of the complement system, but it also inhibits factor XIIa and kallikrein. Mutations and deficiency of C1-INH and factor XIIa results in dysregulated bradykinin production, which increases vascular permeability, leading to angioedema as seen in hereditary angioedema (HAE; for a review, see Cugno et al. 2009 ). HAE also underscores the interaction of the proteins involved in the complement, coagulation and contact proteolytic cascades.