In obesity, liver CYP2R1 mRNA expression and protein levels are reduced by 40% and 50%, respectively, leading to a 70% decrease in 25‐hydroxylase activity (p < 0.01) and ~20% lower serum 25‐hydroxyvitamin D (25OHD) levels. Here, CYP2R1 is linked to obesity due to melanocortin 4 receptor deficiency.