Biglycan, also known as PG I, is a secreted chondroitin/dermatan sulfate proteoglycan in the small leucine-rich proteoglycan (SLRP) family. SLRP family members are characterized by N-terminal and C-terminal cysteine-rich domains that flank the central region containing 10-12 tandem leucine-rich repeats (LRRs). Biglycan function is important in the development and maintenance of many tissues (1). The human Biglycan cDNA encodes a 368 amino acid (aa) precursor with a 19 aa signal sequence and a 18 aa propeptide that is cleaved by BMP-1 (2). Mature human Biglycan shares 97% aa sequence identity with bovine, mouse, and rat Biglycan. The mature protein can be further cleaved by proteases, which compromises its inability to bind to other molecules (3, 4). The 45 kDa core protein is approximately one third the molecular weight of the fully glycanated form and can assemble into noncovalently-associated dimers (5). Biglycan binds, crosslinks, and stabilizes several proteins in the collagen matrix (6). It also binds and modulates the activity of a variety of non-matrix proteins, including C1q, collectins, TGF-beta, and Wnt3a (3, 7, 8). Biglycan binds to TLR2, TLR4, P2X4, and P2X7, leading to the increased production of inflammatory mediators, the migration of vascular endothelial cells, and the enhancement of oxidized LDL induced aortic valve calcification (9 - 11). Biglycan also blocks the uptake and degradation of acetylated LDL in atherosclerotic plaques by binding to SR-A (12). It stabilizes the neuromuscular junction through interactions with MuSK as well as alpha- and gamma-Sarcoglycan (13).