LRP5 (LDL receptor related protein 5) is a transmembrane coreceptor that plays critical roles in Wnt signaling pathway activation and bone metabolism. LRP5 functions as a coreceptor with frizzled receptors to transduce canonical Wnt signals, promoting β-catenin stabilization and TCF/LEF-mediated transcription 1. The protein is essential for bone homeostasis, where it regulates osteoblast function and bone mineral density. Mutations in LRP5 are associated with diverse skeletal disorders, including osteoporosis-pseudoglioma syndrome in compound heterozygous patients, who exhibit severe bone loss and vitreoretinal abnormalities 2. Common polymorphisms, particularly rs3736228 C>T, increase susceptibility to osteoporosis and fractures across multiple populations 3. LRP5 variants also affect cortical bone architecture, with certain polymorphisms associated with reduced cortical bone area and thickness in women 4. Beyond skeletal functions, LRP5 contributes to retinal vascular development through norrin signaling and is implicated in familial exudative vitreoretinopathy 5. Recent studies reveal LRP5's role in metabolic regulation, with increased placental expression in gestational diabetes 6, and its interaction with SELENOP in colorectal cancer progression through Wnt pathway modulation 7. These findings establish LRP5 as a multifunctional coreceptor critical for skeletal, ocular, and metabolic health.