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). This evidence concerns the gene KLK4 and hereditary angioedema.