In particularly, this pathway is required for commitment of mesenchymal stem cells to the OB lineage, and OB precursor cell proliferation and differentiation.1–3 Notice that loss-of-function of LRP6 in humans leads to multiple disorders, including triglycerides, hypertension, diabetes, and osteoporosis.4 Loss-of-function of LRP5 is found to cause osteoporosis-pseudoglioma syndrome,5,6 while gain-of-function mutations in LRP5 induced high bone mass.7,8 These observations provide compelling evidence for LRP5/6’s function in bone mass homeostasis. Here, LRP6 is linked to osteoporosis.