Ptgir, the prostaglandin I2 receptor gene, encodes a G protein-coupled receptor. It is a key player in the prostacyclin (PGI2) signaling pathway, which is crucial for maintaining tissue homeostasis in response to physiologic or pathophysiologic stress. PGI2-Ptgir signaling is involved in various biological processes such as vascular remodeling, cell-cell communication, and immune regulation [1,3,4,5]. Genetic models, like Ptgir-deficient mice, have been valuable for studying its functions.

In renal fibrosis, deletion of the Ptgir gene in collagen-producing fibroblastic cells aggravated renal fibrosis, indicating that Ptgir activation by PGI2 protects the kidney from fibrosis by inhibiting fibroblast over-activation [2]. In fibromuscular dysplasia (FMD), rare loss-of-function mutations of Ptgir were enriched among FMD patients, suggesting a role for Ptgir-mediated prostacyclin signaling in non-atherosclerotic stenosis and dissection [3]. In CD8 T cell exhaustion, PTGIR, as an NRF2-regulated protein, promotes CD8 T cell dysfunction, and silencing PTGIR expression restores the anti-tumor function of KEAP1-deficient T cells [4].

In conclusion, Ptgir is essential in multiple biological processes and disease conditions. Gene-knockout models of Ptgir have significantly contributed to understanding its role in renal fibrosis, FMD, and CD8 T cell-related immune evasion, providing potential therapeutic targets for these diseases.