GPC4 (glypican 4) is a cell surface heparan sulfate proteoglycan that functions as a GPI-anchored protein involved in multiple physiological and pathological processes 1. Primary function: GPC4 acts as a coreceptor in developmental signaling pathways, with roles in kidney tubule and central nervous system development 2. Mechanism: GPC4 participates in Wnt signaling and can bind APOE4 to modulate receptor trafficking 3. In colorectal cancer, CD36-mediated ubiquitination of GPC4 suppresses β-catenin/c-myc signaling and inhibits glycolytic gene expression 4. Disease relevance: GPC4 variants cause Keipert syndrome, characterized by craniofacial and digital abnormalities resulting from loss-of-function mutations that impair protein stability and proper glycosylation 1. In Alzheimer's disease pathology, Aβ-induced microglial GPC4 upregulation exacerbates tau hyperphosphorylation and neuronal tau toxicity, particularly in APOE4 carriers 3 5. Clinical significance: GPC4 represents a molecular link between amyloid and tau pathology in neurodegeneration. In inflammatory uveitis, FTO-mediated m6A modification of GPC4 regulates microglial inflammation through TLR4/NF-κB signaling, suggesting therapeutic targeting potential 6. The tight clustering of GPC3 and GPC4 on Xq26 may explain phenotypic variability in growth dysregulation syndromes 2.