CASR and hypercalcemia disease: Interestingly, hypercalcemia also disrupts intracellular Ca2+ homeostasis [24], with Ca2+ homeostasis modulator 1 (CALHM1), a non-selective voltage- and Ca2+-dependent cation channel, and calcium sensing by CaSR (calcium-sensing receptor) now recognized as key mediators of extracellular Ca2 effects on neuronal excitability and synaptic transmission [21,25].