Perforin 1 (PRF1) (PRF1)

Perforin 1 (PRF1) is a specialized pore-forming protein primarily produced by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells (UniProt: P14222). Upon immune recognition of a target cell, such as a tumor cell, perforin is released from secretory granules into the immunological synapse. In the presence of calcium, perforin monomers bind to the target cell's plasma membrane and oligomerize to form large transmembrane pores (PMID: 20107435). These pores disrupt the membrane's integrity and serve as a gateway for granzymes to enter the target cell and initiate apoptosis (PMID: 27181362). This mechanism is fundamental to the body's defense against malignancy and viral infections. Mutations in the PRF1 gene are the primary cause of familial hemophagocytic lymphohistiocytosis type 2, while its dysregulation is linked to various autoimmune and inflammatory diseases. In modern oncology, perforin is the critical effector molecule for many immunotherapies, including CAR-T cells and bispecific antibodies, which aim to direct perforin-mediated lysis toward cancer cells (PMID: 24553151).

Other names

PerforinPore-forming proteinPFPCytolysinHPLH2P1

Perforin inhibitors prevent the calcium-dependent oligomerization of monomers into pores, while immunotherapies utilize perforin to create pores in tumor cell membranes for granzyme delivery.