CYP2R1 and Sepsis: In cases of severe infection (such as sepsis), which can cause impaired liver function (39), the decline in 25(OH)D levels may result from the downregulation of CYP2R1 and CYP27A1 (another 25-hydroxylase), coupled with the upregulation of the catabolic enzyme CYP24A1 (40, 41).