With this hypothesis, we have delineated the pathogenesis of Camurati–Engelmann disease (CED), in which mutations in the LAP cause conformational dissociation,223 resulting in increased release of activated TGF-β1 and distortion of the resorption-induced TGF-β1 gradients. This evidence concerns the gene TGFB3 and cranioectodermal dysplasia.