Other open questions pertaining to the unique MC4R system await structural elucidation, such as determining the apo-state conformation, dimer-arrangements relevant to MC4R as an endocrine GPCR,49 and MC4R bound with endogenous ligands such as α-, β-MSH, AgRP or the cofactor protein MRAP.50 Altogether, the structural findings presented here will facilitate the development of new MCR subtype- and G-protein-selective anti-obesity drugs. Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.