Perforin (PRF) is a member of the MACPF (membrane-attack-complex-perforin) domain protein family, which we have recently discovered have the same molecular fold as bacterial cholesterol-dependent cytolysins (1).PRF is expressed in cytotoxic lymphocytes, where it is sorted to the lumen of secretory granules.Calcium-dependent pore-forming properties of PRF are essential for the delivery of pro-apoptotic granule serine proteases, granzymes, into the cytoplasm of virus-infected or transformed target cell, where they trigger apoptosis (2).Numerous studies have shown that PRF-deficient mice are markedly immunosuppressed and the majority develop spontaneous, aggressive disseminated B-cell lymphoma as they age (3).In humans, congenital PRF deficiency leads to Familial Haemophagocytic Lymphohistiocytosis (FHL), a potentially fatal immune deficiency disorder (3-5).In milder cases it may predispose an individual to haematological cancers (4).