SMO is involved in Hedgehog (HH) signalling, which is important in cell patterning and differentiation, including vertebrate limbs,58 is associated with tissue damage repair and is activated in osteoarthritis cartilage.59 The genetic effect of rs143083812 and the association with osteoarthritis could be due to direct perturbation of the cholesterol-binding region in SMO via the p.Arg173Cys substitution,56 which activates SMO and results in increased HH activity. Here, SMO is linked to osteoarthritis.