Agrin is a 400-600 kDa heparan sulfate proteoglycan component of the extracellular matrix. Multiple forms of are generated by alternative splicing and proteolytic cleavage. Agrin binds to BMP-2, BMP-4, and TGF-beta, and it blocks BMP-induced signaling through BMPR-IA. Agrin binds to a complex of alpha-Dystroglycan, MuSK, and LRP4 on myotubes and induces the clustering of AChR and motoneuron-myotube adhesion at the neuromuscular junction. It binds the Abeta (1-40) peptide in Alzheimerâs disease plaques, promotes amyloid fibril formation, and regulates neuronal excitability. It also binds the gp41 coat protein of HIV-1 and functions as an epithelial cell-virus attachment receptor. During T cell activation, Agrin contributes to formation of the immunological synapse and regulates the threshold of T cell activation. Agrin is upregulated in hepocellular carcinoma, where it enhances cell proliferation and tumor progression.