Perforin is contained within these granules and upon release forms pores in target cell membranes, allowing the passage of granzymes which initiate apoptotic pathways, eventually leading to target cell death.4 Mutations in the perforin gene (PRF) lead to failure of pore formation and target cell cytotoxicity in effector cells, resulting in proliferation of highly activated cytotoxic T and NK cells, which in turn lead to hypercytokinemia and the subsequent clinical sequelae of HLH. The gene discussed is PRF1; the disease is hemophagocytic syndrome.