In conjunction with our previous findings in fetal mouse epithelial buds10 that activation of the CaSR leads to Ca2+i mobilisation, we propose that, in the developing human lung epithelium, CaSR activation by NPS R-568 and/or fetal hypercalcemia leads to an increase in Ca2+i, attendant activation of AC1 and opening of CFTR. Here, ADCY1 is linked to hypercalcemia disease.