Thus, reduced uptake of VDBP/25-OHD by megalin in diabetic nephropathy could lead to intrarenal losses of VDBP and vitamin D. To better understand the renal response to and the consequences of diminished endocytic ligand functioning in the context of diabetes, we have studied, longitudinally, nephropathy-prone DBA/2J diabetic mice to explore if megalinuria occurs in an albuminuric murine model of T1D and if it is associated with abnormal intrarenal vitamin D homeostasis. Here, LRP2 is linked to diabetes mellitus.