555118646ENSG00000180644ENSMUSG00000037202P14222P10820NM_005041NM_001083116NM_011073NP_001076585NP_005032NP_035203Perforin-1 Perforin (PRF), encoded by the PRF1 gene, is a pore-forming toxic protein housed in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells.

[6] Purifying perforin is challenging due to its tendency to lose activity and stability in solution, and only recently has a recombinant form been successfully produced.

[11] The initial concept of a plasma membrane pore model was challenged when research revealed that granzyme B could undergo endocytosis independently of perforin.

[14] Around the turn of the 21st century, it was recognized that a total loss of perforin activity leads to a severe, fatal autosomal recessive immunoregulatory disorder in infants, known as familial hemophagocytic lymphohistiocytosis (FHL), typically appearing before 12 months of age.

[5] Sub-acute perforinopathies encompass a diverse array of symptoms, all stemming from a partial ("sub-total") reduction in cytotoxic lymphocyte (CL) activity due to bi-allelic mutations in one of the four previously mentioned genes.

In contrast to the acute form, diagnosing sub-acute perforinopathies can be challenging due to their typically milder and more sporadic clinical manifestations, an intermittent disease course, variability in onset age, and their frequent positive response to non-specific immune-suppressive or immune-ablative treatments.

[5] Chronic perforinopathies are regarded as a range of immune-related conditions resulting from monoallelic mutations in genes linked to familial hemophagocytic lymphohistiocytosis (FHL).