OXGR1 is a G protein-coupled receptor that serves as a metabolite sensor for dicarboxylates, particularly α-ketoglutarate (α-KG) and the inflammatory mediator leukotriene E4 (LTE4) 1. The receptor recognizes α-KG through a bipartite-acid pocket with primary and accessory binding sites, while LTE4 binds at a distinct site between transmembrane domains 3-5 1. Both ligands activate OXGR1 primarily through Gq signaling, with LTE4 additionally inducing Gi activation 1. OXGR1 functions in multiple physiological contexts. In the distal nephron, α-KG-stimulated OXGR1 activates pendrin-expressing intercalated cells to drive electroneutral NaCl reabsorption and bicarbonate secretion during metabolic alkalosis 2. In respiratory epithelium, itaconate binding to OXGR1 triggers intracellular Ca2+ release supporting mucociliary clearance [UniProt summary]. LTE4 activation induces mucin release from pulmonary epithelium in response to fungal allergens [UniProt summary]. Loss-of-function OXGR1 variants are associated with calcium oxalate nephrolithiasis and nephrocalcinosis, with six deleterious missense variants identified in unrelated families demonstrating impaired α-KG-dependent calcium uptake 3. Recently, α-KG/OXGR1 signaling in vascular smooth muscle was identified as therapeutic target for rosacea erythema through promotion of vascular contraction 4. Additionally, tumor-derived α-KG activating OXGR1 on macrophages promotes immune escape in cholangiocarcinoma 5.