• CDH19 deficiency impairs osteoblast proliferation and differentiation, leading to reduced bone mass and deteriorated bone microstructure in mice.
• The PI3K/AKT signaling pathway is identified as a critical downstream mediator of CDH19's effects on osteogenesis.
• Pharmacological activation of PI3K/AKT with 740Y-P partially rescues the osteogenic defects caused by CDH19 deletion, suggesting a potential therapeutic strategy.
• CDH19 emerges as a novel molecular target for treating osteoporosis and other bone diseases.