Finding a balance between protection and pathology: The dual role of perforin in human disease

Robin C. Willenbring, Aaron J. Johnson

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations


Perforin is critical for controlling viral infection and tumor surveillance. Clinically, mutations in perforin are viewed as unfavorable, as lack of this pore-forming protein results in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). However, many mutations in the coding region of PRF1 are not yet associated with disease. Animal models of viral-associated blood-brain barrier (BBB) disruption and experimental cerebral malaria (ECM) have identified perforin as critical for inducing pathologic central nervous system CNS vascular permeability. This review focuses on the role of perforin in both protecting and promoting human disease. It concludes with a novel hypothesis that diversity observed in the PRF1 gene may be an example of selective advantage that protects an individual from perforin-mediated pathology, such as BBB disruption.

Original languageEnglish (US)
Article number1608
JournalInternational journal of molecular sciences
Issue number8
StatePublished - Aug 2017


  • Blood-brain barrier disruption
  • Familial hemophagocytic lymphohistiocytosis type 2
  • Perforin
  • Selective advantage
  • Single nucleotide variants

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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