Irf1, the interferon regulatory factor 1, was initially recognized as a nuclear factor binding and activating type I interferon gene promoters. It is involved in a wide array of biological functions, especially in the context of innate immune responses against pathogens, and also plays a role in regulating cell death, self-renewal, and stress responsiveness in hematopoietic stem cells [1,6,7]. It is conserved throughout vertebrate evolution and has been linked to various pathways, such as those related to antiviral responses, inflammation, and cell death regulation [1,5]. Genetic models, like knockout (KO) mouse models, have been crucial in understanding its functions.

In terms of disease-related findings, in endometrial cancer, wild-type SPOP binds to IRF1, leading to its degradation and suppressing PD-L1 expression. However, EC-associated SPOP mutants stabilize IRF1, upregulating PD-L1 and promoting tumor immune escape [4]. In osteoarthritis, the IRF1/GBP5 axis promotes disease progression by activating chondrocyte pyroptosis, and IRF1 also governs the expression of SMARCC1 via the GCN5-SETD2 axis, facilitating M1 skewing of macrophages and contributing to OA advancement [3,8]. In radiation-induced responses, IRF1 activation in structural cells promotes inflammation, and its genetic deletion or pharmacological inhibition tempered radiation-induced inflammatory cell death [2].

In summary, Irf1 is a key regulator in multiple biological processes. Its functions are crucial in diseases like cancer, osteoarthritis, and radiation-induced inflammatory responses. The use of Irf1 KO mouse models has significantly contributed to understanding its role in these disease conditions, providing potential therapeutic targets for treatment [2,3,4,8].