Gαs signaling has been shown to inhibit Hh signaling downstream of Smo by inhibiting Gli activities during ectopic bone formation in POH patients and in brain tumors.1,26 It is likely that the role of Gαs signaling in ectopic bone formation reflects its underappreciated function in regulating normal intramembranous ossification through inhibiting Hh signaling, as both ectopic bone in POH and normal cranial bones undergo intramembranous ossification. The gene discussed is SMO; the disease is progressive osseous heteroplasia.