The defect of C1INH comprises either a deficiency (type I C1INH-HAE) or a dysfunction (type II C1INH-HAE) of the protein, allowing for a dysregulated plasma kallikrein activity within the kallikrein–kinin pathway, and thus for the overproduction of bradykinin with, in turn, the consequent activation of the bradykinin B2 receptors (1, 2). The gene discussed is KNG1; the disease is hereditary angioedema.