However, a decrease in 25(OH)D endocytosis and a very significant increase in urine were also observed in KO mice, so it is believed that the balance between 25(OH)D and stimulation of 1-α-hydroxylase, both produced by a loss of ClC-5 function, would determine the presence or absence of hypercalciuria and that this balance could depend on genetic or nutritional factors [3,11,12,49,50]. The gene discussed is CLCN5; the disease is Hypercalciuria.