ERRα, a master regulator of mitochondrial biogenesis and energy metabolism, is targeted by inverse agonists (compound <b>29</b>, GSK5182) and agonists (JND003, SLU-PP-915), which show promise in ameliorating insulin resistance and promoting lipid oxidation in preclinical obesity models. Here, ESRRA is linked to obesity due to melanocortin 4 receptor deficiency.