LRP5 and hyperphosphatemia: The predisposition of the basal ganglia region for calcification has been explained by a “two-hit mechanism.”(150,151) The “first-hit” is increased expression of several pro-osteogenic molecules (osteonectin, β-catenin, klotho, frizzled-4, ecto-5’-nucleotidase, low-density lipoprotein receptor-related protein 5 [LRP5], Wnt3A, and type 1 collagen) and the presence of neuroprogenitor cells in the basal ganglia.(151) Hyperphosphatemia, resulting from the lack of PTH, constitutes the “second-hit” leading to BGC in hypoparathyroidism.