Loss of function of LEMD3 results in unique sclerosing bone disease spectrums, osteopoikilosis (MIM #166700), melorheostosis (MIM #155950) and Buschke-Ollendorff syndrome (BOS; MIM #166700) (Table 2).306,307 LEMD3 has been shown to antagonize BMP and TGF-β by interacting with SMAD-1, -2, -5, and -9. This evidence concerns the gene LEMD3 and Buschke-Ollendorff syndrome.