Interestingly, either activation of the catabolic enzyme CYP24A1 by calcidol or calcitriol or inactivation of CYP27B1 by calcitriol can lead to a negative feedback loop to regulate the vitamin D level, broadening the role of CYP24A1 as an important mediator of the rate limiting step of not only vitamin D generation but also hormone self-regulation, thus potentially ameliorating hypercalcemia. This evidence concerns the gene CYP24A1 and hypercalcemia disease.