PTH1R and hypercalcemia disease: PTH1R plays critical roles in regulation of calcium metabolism, skeletal development, and homeostasis.1–10 Abnormalities in PTH/PTHrP/PTH1R signaling cause human diseases, such as hypercalcemia, osteoporosis, tumorigenesis, and metastasis.11,12 Therefore, it is important to understand how PTH1R is regulated under physiological and pathological conditions.