CaSR is expressed on the basolateral membrane in the thick ascending limb of Henle loop (left panel) and in the cortical distal convoluted tubule (right panel). In the thick ascending limb of Henle loop, CaSR inactivates the luminal potassium recycling through the ROMK channels. This effect dissipates the positive luminal electrical potential that is the driving force for passive paracellular calcium reabsorption. In this nephron segment, CaSR also inhibits the phosphorilation of caludin-16, which can be expressed in tight junctions only after phosphorilation. The absence of claudin-16 reduces the tight junction permeability to calcium and magnesium and, as a consequence, passive calcium reabsorption.In the cortical distal convoluted tubule, CaSR reduces calcium pump activity (PMCA) and calcium active reabsorption.PLA2 is phospholipase A2, AA is arachidonic acid, 20-HETE is 20-hydroxi-eicosa-tetraenoic-acid, PLC is phospholipase C, PKA is protein kinase A. Split lines express the enhancing (plus sign) or inhibitory (minus sign) pathways activated by CaSR.