Apart from their function in cellular metabolism, one of the PDKs, pyruvate dehydrogenase kinase 4 (PDK4), has been reported to localize at the ER-mito contact sites of muscle cells, regulating the insulin signaling during obesity [29], suggesting an unexplored role for this mitochondrial protein in cellular physiology. Here, PDK4 is linked to obesity due to melanocortin 4 receptor deficiency.