EXT1 and Osteochondroma: Although Ext1/2 KO mice develop skeletal lesions similar to osteochondroma in HME with an abnormal extracellular distribution of Hh ligands [107], recent studies have demonstrated that the autosomal dominant disorder metachondromatosis (MC; OMIM 156250), a rare disease characterized by enchodroma and osteochondroma, is found to be involved in heterozygous loss-of-function mutations in tyrosine-protein phosphatase non-receptor type 11 (PTPN11), encoding protein tyrosine phosphatase SHP2 that relays signals from the activated Ras/extracellular signal-regulated kinase (ERK) pathway [98,103].