In the last few years, insight into their endogenous roles has come from two rare diseases: hyaline fibromatosis syndrome, caused by mutations in CMG2, and growth retardation, alopecia, pseudo-anodontia, and optic atrophy (GAPO) syndrome, caused by loss-of-function mutations in TEM8. This evidence concerns the gene ANTXR2 and Leber hereditary optic neuropathy.