In osteoarthritis, the material properties of the cartilage ECM deteriorate as chondrocytes inappropriately shift the balance from canonical (Alk5/Smad2/3) to non-canonical (Alk1/Smad1/5/8) TβRI signaling (Blaney Davidson et al., 2009). The gene discussed is TGFBR1; the disease is osteoarthritis.