A sizeable fraction of circulating testosterone is bound to sex hormone-binding globulin (SHBG); however, it is still not established if the observed link between the total testosterone and several cardiovascular risk factors (atherogenic lipid profile, type 2 diabetes, obesity) mirrors an effect of free circulating testosterone, or whether SHBG plays a more direct role. The gene discussed is SHBG; the disease is obesity due to melanocortin 4 receptor deficiency.