CREBBP and cleidocranial dysplasia 1: TAK1 acts as a central node in BMP–MAPK crosstalk.237TAK1 deficiency in osteoblasts leads to striking skeletal abnormalities, including clavicular hypoplasia and delayed fontanelle fusion, which are phenotypes that closely resemble human cleidocranial dysplasia caused by RUNX2 haploinsufficiency.83 Mechanistically, TAK1 orchestrates osteoblast differentiation through the TAK1–MKK3/6–p38 MAPK axis, which phosphorylates Runx2 and enhances its transcriptional activity by facilitating its interaction with the coactivator CREB-binding protein (CBP)/p300.83