The extracellular matrix (ECM) plays a crucial role in cell behavior beyond providing structural support. ECM proteins, which are large and complex with multiple conserved domains, bind adhesion receptors like integrins and soluble growth factors, regulating their distribution and activation. These proteins can integrate complex, multivalent signals into cells in a spatially organized manner. The article explores the functions of ECM proteins in binding and presenting growth factor signals, highlighting their roles in developmental patterning, stem cell niches, cancer, and genetic diseases. It discusses the specific binding of growth factors to ECM proteins, such as fibronectin and vitronectin, and the regulation of TGF-β by ECM proteins. The article also suggests that ECM proteins can act as localized, multivalent signal integrators, organizing receptors into complexes that enhance membrane-proximal regulation and integrate signals transduced by these receptors. The implications of these findings for future research and clinical applications are discussed, emphasizing the importance of further investigation into the roles of ECM proteins in signaling events.The extracellular matrix (ECM) plays a crucial role in cell behavior beyond providing structural support. ECM proteins, which are large and complex with multiple conserved domains, bind adhesion receptors like integrins and soluble growth factors, regulating their distribution and activation. These proteins can integrate complex, multivalent signals into cells in a spatially organized manner. The article explores the functions of ECM proteins in binding and presenting growth factor signals, highlighting their roles in developmental patterning, stem cell niches, cancer, and genetic diseases. It discusses the specific binding of growth factors to ECM proteins, such as fibronectin and vitronectin, and the regulation of TGF-β by ECM proteins. The article also suggests that ECM proteins can act as localized, multivalent signal integrators, organizing receptors into complexes that enhance membrane-proximal regulation and integrate signals transduced by these receptors. The implications of these findings for future research and clinical applications are discussed, emphasizing the importance of further investigation into the roles of ECM proteins in signaling events.