PAMs, such as NPS-R568 and cinacalcet, enhance CaSR activity, leading to increased blood calcium levels and treat conditions like osteoporosis.153 In contrast, NAMs such as NPS-2143 inhibit CaSR activity, reducing sensitivity and aiding in the treatment of hypercalcemia-related disorders.154 In addition, magnesium can bind to CaSR, triggering intracellular calcium signaling and the phosphorylation of ERK1/2, which promotes osteoblast differentiation and new bone formation.155,156. The gene discussed is CASR; the disease is osteoporosis.