PRF1

PRF1 refers to the human gene that encodes perforin, a cytolytic pore-forming protein essential for immune surveillance. It is expressed in cytotoxic T lymphocytes and natural killer cells and participates in eliminating virally infected and malignant cells. The PRF1 gene is part of the human genome; the protein is stored in cytotoxic granules and released upon immune activation.

Perforin binds to target cell membranes in the presence of calcium, oligomerizes to form transmembrane pores, and enables granzymes to enter the target cell to trigger apoptosis. Perforin works in concert with granzymes A and B, with expression primarily in cytotoxic lymphocytes and to a lesser extent in other immune cells.

Mutations in PRF1 are associated with familial hemophagocytic lymphohistiocytosis type 2 (FHL2), an autosomal recessive disorder characterized by uncontrolled immune activation. Pathogenic variants reduce perforin expression or function, leading to impaired cytotoxicity and persistent immune stimulation. Carriers may be asymptomatic.

Clinically, PRF1-related disease is diagnosed by genetic testing for PRF1 variants, assessment of perforin expression in natural killer and T cells when available, and HLH diagnostic criteria. Management of HLH involves supportive care and immunochemotherapy; definitive therapy typically includes hematopoietic stem cell transplantation. Ongoing research explores gene therapy and other targeted treatments.