The calcium-sensing receptor (CASR) is a G-protein-coupled receptor that detects extracellular calcium concentration fluctuations and maintains calcium homeostasis 1. CASR functions as a homodimer with an extracellular Venus Flytrap domain containing calcium-binding sites and a seven-transmembrane domain 2. The receptor employs a co-agonist mechanism, with aromatic amino acids like tryptophan acting with divalent cations (calcium or magnesium) to achieve full activation 3. CASR demonstrates promiscuous G-protein coupling, binding Gq, Gi, and Gs proteins through a common mode involving intracellular loops and the C-terminal helix 1. In parathyroid glands and kidney, elevated circulating calcium activates CASR, suppressing parathyroid hormone (PTH) secretion and regulating renal tubular calcium resorption 4. Dysfunction of CASR causes multiple disorders: gain-of-function mutations cause autosomal dominant hypocalcemia, while loss-of-function mutations lead to familial hypocalciuric hypercalcemia 5. Recent evidence identifies CASR signaling through diacylglycerol kinase δ (DGKD) as a key pathway in kidney stone disease susceptibility; reduced CaSR signaling increases stone risk, potentially reversible by calcimimetic drugs 6.