SOX9 and Menkes disease: The skeletal phenotypes associated with MD are mainly caused by GOF mutations in the TRPV4 gene, which not only activate calcium channels and lead to dysregulation of intracellular Ca2+ ion levels, but also up-regulate SOX9 expression and lead to abnormal chondrocyte differentiation.[15,16] Han et al[17] showed that the GOF variant in the TRPV4 gene disrupted osteoblast differentiation by increasing the activity of the Ca2+/NFATc1 pathway and induced the endochondral ossification disorders associated with MD.