Loss of Sc5d results in micrognathia due to a failure in osteoblast differentiation

•Sc5d-/- mice exhibit mandibular hypoplasia resulting from defects in osteoblast differentiation.•Cholesterol metabolism plays a crucial role in bone development through the formation of primary cilium, a cell surface structure that senses extracellular cues.•The activation of hedgehog and WNT/β-catenin signaling pathways, which induce expression of osteogenic genes Col1a1 and Spp1, is compromised in the mandible of Sc5d-/- mice.•Treatments with an inducer for hedgehog or WNT/β-catenin signaling or simvastatin, a drug that restores abnormal cholesterol productions, partially rescue the defects in osteoblast differentiation seen in Sc5d-/- cells.