AVPR2 and hereditary disease: For instance, the active state structure of V2R complexed with Gs protein helped to explain how the V2R R137H or R137 L/C variants could lead to two severe genetic diseases (Bous et al., 2021), and the MC4R structure helped to explain how Ca2+ is required for agonist, but not antagonist efficacy (Israeli et al., 2021).