C1-INH concentrate for HAE episodes was first described in 1973, and there are two plasma-derived formulations currently available (Berinert and Cinryze), as well as one recombinant form (Ruconest), all administered intravenously.1–5,7,8,135,136,148 They are currently approved for acute HAE, although these medications have been used for ACEi-mediated forms.1–5,7,8,135,136,148 Berinert and Cinryze provide native plasma protein that regulates kallikrein and Factor XII activity, reducing bradykinin production. The gene discussed is KLK4; the disease is hereditary angioedema.