OXGR1, also known as 2-oxoglutarate receptor 1, is a G-protein-coupled receptor (GPCR) that plays crucial roles in various biological processes. It is involved in metabolic regulation, immune response, and ion transport. The ligands of OXGR1, such as itaconate and α-ketoglutaric acid (AKG), activate the receptor, leading to downstream signaling pathways like Ca2+ mobilization, ERK phosphorylation, and activation of the PI3K/AKT pathway [1,2,3]. OXGR1 is important for maintaining physiological homeostasis in the body and genetic models have been instrumental in understanding its functions.

In KO/CKO mouse models, OXGR1 knockout results in skeletal muscle atrophy, decreased capillary density, and endurance exercise capacity, indicating its role in regulating skeletal muscle blood flow and metabolism [4]. In epididymal-specific OXGR1 knockdown models, OXGR1 is shown to be essential for epididymal sperm maturation and fluid acid-base balance [5]. In Goldblatt hypertensive mice, OXGR1-dependent (pro)renin receptor upregulation in the collecting ducts of the clipped kidney contributes to Na+ balance and blood pressure regulation [6].

In conclusion, OXGR1 is a key receptor involved in multiple biological functions including muscle development, sperm maturation, and sodium balance. Studies using KO/CKO mouse models have significantly enhanced our understanding of its role in these processes and related disease conditions such as hypertension, skeletal muscle-related disorders, and male infertility.