1,25-dihydroxy Vitamin D2 is the active circulating metabolite of vitamin D2 formed by 25-hydroxylase in the liver and 25-hydroxyvitamin D-hydroxylase in the kidney. By binding to the vitamin D receptor (VDR), 1,25-dihydroxy Vitamin D2 activates VDR to interact with the retinoid X receptor (RXR), forming the VDR/RXR/cofactor complex, which regulates gene transcription. Because 1,25-dihydroxy Vitamin D2 circulates at picomolar concentrations and is highly lipophilic, it is difficult to quantify.