Prf1, encoding the pore-forming protein perforin, is crucial in the immune system. It is involved in cytotoxic T-lymphocyte and natural killer cell-mediated immune responses, where it forms pores in target cell membranes, facilitating the entry of granzymes and subsequent apoptosis of infected or cancerous cells [3]. This process is integral to the body's defense against pathogens and tumor surveillance.

Mutations in Prf1 are strongly associated with hemophagocytic lymphohistiocytosis (HLH), a severe hyperinflammatory syndrome. A meta-analysis indicated that the PRF1 Ala91Val polymorphism affects the risk of developing HLH [2]. A patient with a heterozygous mutation of PRF1: c.674G>A (p.R225Q) was diagnosed with HLH, suggesting this mutation may be a possible pathogenic variant [1]. A 17-year-old male with a homozygous missense mutation (c.1081A>T p.(Arg361Trp)) in the PRF1 gene was diagnosed with familial HLH type 2 with CNS involvement [4]. A 20-year-old female with two heterozygous missense variants in the PRF1 gene (A91V and R104C) on exon 2 was diagnosed with primary HLH [5].

In conclusion, Prf1 is essential for the cytotoxic function of immune cells. The study of Prf1, especially through the identification of its mutations in patients, has significantly contributed to our understanding of HLH, a life-threatening hyperinflammatory disease. These findings highlight the importance of Prf1 in maintaining immune homeostasis and the potential implications of its dysfunction in disease development.