MESD (mesoderm development LRP chaperone) functions as a specialized endoplasmic reticulum chaperone that facilitates proper folding and trafficking of LRP5 and LRP6, the co-receptors for canonical Wnt signaling 1. MESD contains two functional domains: a chaperone domain that maintains the β-propeller domain of LRP5/6 in a folding-competent state, and an escort domain that ensures safe trafficking from the ER to Golgi while preventing premature ligand binding 1. Additionally, MESD acts as a direct chaperone for type I collagen (COL1A1), with proper ER localization being essential for preventing cytosolic protein aggregation 2. Beyond its chaperone role, mature MESD can bind to LRP5/6 at the cell surface and function as a universal inhibitor of Wnt signaling by blocking both Wnt agonists and antagonists 3. Mutations in MESD cause osteogenesis imperfecta type XX, a bone fragility disorder 42. The pathogenic mutations are hypomorphic alleles that disrupt ER retention, leading to reduced but not completely eliminated LRP5/6 trafficking 4. This results in impaired Wnt signaling affecting bone formation and dental development, as these processes appear more sensitive to reduced canonical Wnt signaling than other developmental pathways 4.