OXGR1, also known as 2-oxoglutarate receptor 1, is a G protein-coupled receptor (GPCR). It plays crucial roles in multiple biological processes, with its ligands like itaconate (ITA) and α-ketoglutaric acid (AKG) involved in various signaling pathways. It is associated with pathways such as PI3K/AKT and is important for functions like cell proliferation, immune response, and metabolic regulation [1,2,4].

In a mouse model of pulmonary infection, ITA was identified as an orthosteric agonist of OXGR1, and ITA-stimulated Oxgr1 was shown to promote mucus secretion and transport in respiratory epithelium, which is vital for the pulmonary innate immune response [1]. In muscle-related studies, AKG stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation in mice. Loss-of-function and gain-of-function mouse models demonstrated that OXGR1 is essential for AKG-mediated exercise-induced beneficial metabolic effects [2]. In the context of nephrolithiasis, rare, dominant loss-of-function OXGR1 variants identified through exome sequencing were associated with recurrent calcium oxalate nephrolithiasis in families. Wild-type OXGR1-expressing Xenopus oocytes exhibited AKG-responsive Ca2+ uptake, while 5 missense variants from patients with nephrolithiasis showed impaired AKG-dependent Ca2+ uptake, indicating loss of function [3].

In conclusion, OXGR1 is essential for functions in the immune response, metabolism, and cell proliferation. The use of KO/CKO mouse models has significantly contributed to understanding its role in diseases such as pulmonary infections, metabolic disorders, and nephrolithiasis. These studies help in unravelling the complex biological mechanisms associated with OXGR1 and may provide insights for potential therapeutic interventions.