In CKD, where levels of 1,25(OH)2D3 levels are reduced, this would lead to decreased megalin expression, reducing the capacity of renal 25(OH)D3 uptake and further reducing 1,25(OH)2D3 production, propagating the cycle and exacerbating vitamin D deficiency (Figure 4) [123]. The gene discussed is LRP2; the disease is chronic kidney disease.