The absence of a protective effect of C4 deficiency in cerebral IRI confirms the non-protective phenotype of C4 deficiency previously reported in models of myocardial and renal IRI and emphasizes the general importance of a MASP-2-dependent C4-bypass activation route [20, 22, 26]. This evidence concerns the gene C4A and hyperinsulinemic hypoglycemia, familial, 4.