P2rx7, the gene encoding the P2X7 receptor, is a non-selective ligand-gated homotrimeric cation channel [2]. The P2X7 receptor functions as a danger sensor, detecting extracellular nucleotides from injured cells and signaling an inflammatory program to nearby cells. It is expressed in immune cells and plays important roles in pathogen surveillance, cell-mediated responses to infectious organisms, and the inflammatory cascade [1,3]. P2rx7 signaling has also been implicated in other physiological and pathological processes such as pain, CNS and psychiatric disorders, and cancer [3].

In chronic nonbacterial osteomyelitis (CNO), rare presumably damaging P2rx7 variants were identified in patients. Patient-derived monocytes and genetically modified THP-1 cells with these variants showed altered potassium flux, inflammasome assembly, IL-1β and IL-18 release, and pyroptosis, suggesting that P2rx7 variants may be a CNO risk factor [4]. In osteosarcoma, P2rx7 knockout cell lines demonstrated that P2rx7 promotes glucose metabolism and osteosarcoma progression by enhancing c-Myc stabilization, indicating it could be a potential diagnostic and/or therapeutic target [5].

In conclusion, P2rx7 plays a crucial role in inflammation, pathogen response, and is involved in various disease conditions such as CNO and osteosarcoma. The use of gene knockout models in mice has been instrumental in revealing its function in these biological processes and disease states, providing valuable insights for potential therapeutic interventions.