Taking into account the increased plasma levels of total VD3 and 25(OH)D3 in Lgmn−/− mice, together with significantly decreased expression of the VD3 catabolizing enzyme CYP24A1 upon legumain deficiency, decreased renal expression of CYP27B1 mRNA in Lgmn−/− mice could be a feedback mechanism to avoid high levels of 1,25(OH)2D3 production and its associated side effects such as hypercalcemia [53]. This evidence concerns the gene CYP27B1 and Hypercalcemia.