It was first appreciated around the turn of this century that the complete loss of perforin activity results in a fatal, autosomal recessive immunoregulatory disorder of infancy (median age of onset <12 months), familial hemophagocytic lymphohistiocytosis (FHL) (13), which can be cured only by heterologous bone marrow transplantation (14). Here, PRF1 is linked to hemophagocytic syndrome.