Osteoprotegerin (OPG) was initially discovered in 1997 as a key regulator in bone metabolism [1] and has meanwhile been implicated in various human diseases including myocardial infarction, stroke, aortic aneurysm, atrial fibrillation, aortic stenosis, chronic kidney disease, diabetes and its complications, and cancer [2–4]. The gene discussed is TNFRSF11B; the disease is aortic stenosis.