Our observations in Npt2a-/- mice suggest presence of risk factors for renal mineralization in addition to hypercalciuria, and if confirmed in humans our findings may be relevant for the optimization of existing and for the development of novel therapies to prevent nephrolithiasis and nephrocalcinosis in human carriers of NPT2a and NPT2c mutations. The gene discussed is SLC34A3; the disease is nephrolithiasis.