Ifngr1, encoding the interferon gamma receptor 1, is a crucial component of the interferon-γ (IFNγ) signaling pathway. IFNγ signals through a tetrameric receptor complex consisting of two IFN-γR1 chains (encoded by Ifngr1) and two IFN-γR2 chains. This pathway is essential for the innate immune defense against mycobacterial infections, and also plays a role in tumor immunity and inflammation regulation [4].

In cancer research, loss-of-function studies have provided key insights. For example, loss of optineurin in colorectal cancer drives immune evasion and immunotherapy resistance via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation, suggesting that Ifngr1 is vital for maintaining IFNγ and MHC-I signaling integrity in cancer immunity [1].

In macrophages following myocardial infarction, knockout of RNF149 exacerbates cardiac dysfunction due to increased infiltration of pro-inflammatory monocytes/macrophages. RNF149 in infiltrated macrophages restricts inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1, indicating Ifngr1's role in macrophage-driven inflammation and cardiac repair [2].

Also, blocking sphingolipid production in cancer cells enhances anti-tumor immune response partly via IFNγ signaling, as depletion of glycosphingolipids increases surface levels of IFNGR1, which mediates IFNγ-induced growth arrest and pro-inflammatory signalling [3].

In conclusion, Ifngr1 is essential for the IFNγ signaling pathway, playing a crucial role in immune defense against mycobacterial infections. Through gene knockout and other loss-of-function models, its significance in cancer immune evasion, macrophage-driven inflammation, and cardiac repair has been revealed. Understanding Ifngr1 can provide insights into disease mechanisms and potential therapeutic strategies in these areas.