An illustrative example is osteogenesis imperfecta (OI), caused by mutations in collagen I, in which three different mechanisms can contribute to the biological phenotype: structural alterations in the secreted collagen, unfolded protein response, and TGF-β dysregulation (Kojima et al, 1998; Lisse et al, 2008; Grafe et al, 2014). Here, TGFB1 is linked to osteogenesis imperfecta.