Summary: A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.

Top Publications

  1. Ohshima K, Shimazaki K, Kume T, Suzumiya J, Kanda M, Kikuchi M. Perforin and Fas pathways of cytotoxic T-cells in histiocytic necrotizing lymphadenitis. Histopathology. 1998;33:471-8 pubmed
    ..Two molecular mechanisms of T-cell-mediated cytotoxicity, one perforin-based and the other Fas-based, have been demonstrated, and both systems induce apoptosis of the target cells...
  2. Zhu L, Aly M, Wang H, Karakizlis H, Weimer R, Morath C, et al. Decreased NK cell immunity in kidney transplant recipients late post-transplant and increased NK-cell immunity in patients with recurrent miscarriage. PLoS ONE. 2017;12:e0186349 pubmed publisher
    ..late-Tx) with functioning renal transplants showed abnormally low CD56dimCD16+ NK-cells containing both perforin and granzyme (vs HC p = 0.021) whereas RM patients exhibited abnormally high numbers of these cells (vs HC p = 0...
  3. Hodge G, Hodge S, Yeo A, Nguyen P, Hopkins E, Holmes Liew C, et al. BOS Is Associated With Increased Cytotoxic Proinflammatory CD8 T, NKT-Like, and NK Cells in the Small Airways. Transplantation. 2017;101:2469-2476 pubmed publisher
    ..Intracellular cytotoxic mediators (perforin/granzyme B), proinflammatory cytokines (IFNγ/TNFα), and expression of GCR were determined in lymphocytes ..
  4. Palterer B, Brugnolo F, Sieni E, Barilaro A, Parronchi P. Neuromyelitis optica, atypical hemophagocytic lymphohistiocytosis and heterozygous perforin A91V mutation. J Neuroimmunol. 2017;311:10-13 pubmed publisher
    ..hemophagocytic lymphohistiocytosis in a patient with neuromyelitis optica, with multiple triggering factors and carrying the common A91V hypomorphic perforin mutation, that blurs the distinction between primary and secondary forms.
  5. Spicer J, Miller C, O Connor P, Jose J, Huttunen K, Jaiswal J, et al. Substituted arylsulphonamides as inhibitors of perforin-mediated lysis. Eur J Med Chem. 2017;137:139-155 pubmed publisher
    The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored...
  6. Kayagaki N, Yamaguchi N, Nakayama M, Kawasaki A, Akiba H, Okumura K, et al. Involvement of TNF-related apoptosis-inducing ligand in human CD4+ T cell-mediated cytotoxicity. J Immunol. 1999;162:2639-47 pubmed
    ..Human CD4+ T cell clones, HK12 and 4HM1, exhibited perforin-independent and Fas ligand (FasL)-independent cytotoxicity against certain target cells, including T lymphoma (..
  7. Spada F, Grant E, Peters P, Sugita M, Melian A, Leslie D, et al. Self-recognition of CD1 by gamma/delta T cells: implications for innate immunity. J Exp Med. 2000;191:937-48 pubmed
    ..The CD1c-reactive gamma/delta T cells were cytotoxic and used both perforin- and Fas-mediated cytotoxicity. Moreover, they produced granulysin, an important antimicrobial protein...
  8. Bassiri H, Das R, Guan P, Barrett D, Brennan P, Banerjee P, et al. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo . Cancer Immunol Res. 2014;2:59-69 pubmed
    ..In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of TCR signaling, or loss of perforin expression significantly reduce iNKT cell killing...
  9. Voskoboinik I, Whisstock J, Trapani J. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15:388-400 pubmed
    ..lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes...

More Information


  1. Bordbar M, Modarresi F, Farazi Fard M, Dastsooz H, Shakib Azad N, Faghihi M. A case report of novel mutation in PRF1 gene, which causes familial autosomal recessive hemophagocytic lymphohistiocytosis. BMC Med Genet. 2017;18:49 pubmed publisher
    ..Our study identified a rare new pathogenic missense mutation in PRF1 gene in patient with HLH disease and it is the first report of mutation in PRF1 in Iranian patients with this disease. ..
  2. Zeine R, Pon R, Ladiwala U, Antel J, Filion L, Freedman M. Mechanism of gammadelta T cell-induced human oligodendrocyte cytotoxicity: relevance to multiple sclerosis. J Neuroimmunol. 1998;87:49-61 pubmed
    ..The use of Ca2+-free media reduced lysis by up to 50%, but fully blocking gammadelta T cell Perforin release and function by either Ca2+ chelation (Mg2EGTA) or the H+-ATPase inhibitor Concanamycin-A (CMA), ..
  3. Ribeiro A, Laranjeira P, Mendes S, Velada I, Leite C, Andrade P, et al. Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther. 2013;4:125 pubmed publisher
    ..FoxP3), T-bet and GATA binding protein 3 (GATA3), on purified T cells, and tumor necrosis factor-alpha (TNF-?), perforin and granzyme B on purified NK cells...
  4. Jiang Y, Yang M, Sun X, Chen X, Ma M, Yin X, et al. IL-10+ NK and TGF-β+ NK cells play negative regulatory roles in HIV infection. BMC Infect Dis. 2018;18:80 pubmed publisher
  5. Fast L. Recipient CD8+ cells are responsible for the rapid elimination of allogeneic donor lymphoid cells. J Immunol. 1996;157:4805-10 pubmed
    ..The perforin pathway was the predominant pathway used by the recipient CD8+ cells to mediate this elimination.
  6. Stepp S, Dufourcq Lagelouse R, Kumar V. Pillars article: Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999. 286: 1957-1959. J Immunol. 2015;194:5044-6 pubmed
  7. Pellegatta S, Valletta L, Corbetta C, Patanè M, Zucca I, Riccardi Sirtori F, et al. Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma. Acta Neuropathol Commun. 2015;3:4 pubmed publisher
    ..Immunizations led to intratumoral up-regulation of IFN-γ, granzyme-b and perforin-1 and down-regulation of TGF-β2 and IL-10...
  8. Elgizouli M, Logan C, Grychtol R, Rothenbacher D, Nieters A, Heinzmann A. Reduced PRF1 enhancer methylation in children with a history of severe RSV bronchiolitis in infancy: an association study. BMC Pediatr. 2017;17:65 pubmed publisher
    ..In this study we investigated the association between DNA methylation patterns in the perforin gene (PRF1) in childhood and a history of hospitalisation for severe RSV disease in the first two years of life...
  9. Fischer B, Muller B, Fischer K, Baur N, Kreutz W. Acidic pH inhibits non-MHC-restricted killer cell functions. Clin Immunol. 2000;96:252-63 pubmed
    ..Both populations are able to kill tumor cells in a MHC-independent manner via perforin/granzymes or TNFalpha, whereas only IL-2-activated cells can use the killing pathway via Fas/FasL...