PRF1 and Familial hemophagocytic lymphohistiocytosis: In line with the fundamental function of perforin-1 in immunity, deleterious variants in the PRF1 gene in humans lead to an aggressive immunoregulatory disorder called familial hemophagocytic lymphohistiocytosis (FHL, which can be fatal without bone-marrow transplantation) (19, 20), as well as hematological malignancies (21–23).