The increase in vascular permeability that leads to angioedema in HAE is closely associated with the mediators of the contact system, specifically the kallikrein–kinin pathway, where C1-INH plays a critical regulatory role across several physiological pathways, including fibrinolysis, coagulation, the contact system, and the complement system [1,7]. The gene discussed is SERPING1; the disease is angioedema.