The article reviews the assembly of fibronectin (FN) into a fibrillar extracellular matrix (ECM) in multicellular organisms. FN, a ubiquitous ECM glycoprotein, is essential for tissue organization and development. The assembly process involves multivalent interactions between FN dimers and other ECM proteins, initiated by binding to cell surface receptors like α5β1 integrin. Receptor binding triggers FN self-association through the N-terminal assembly domain and promotes actin cytoskeleton organization to enhance cell contractility. Conformational changes in FN expose additional binding sites, facilitating fibril formation and conversion to a stable, insoluble form. The assembled FN matrix impacts tissue organization by contributing to the assembly of other ECM proteins. The review highlights key steps, molecular interactions, and cellular mechanisms involved in FN matrix assembly, emphasizing the importance of integrin binding, conformational changes, and the role of FN in the assembly of other ECM components like type I collagen, microfibrils, and elastic fibers. It also discusses the implications of FN matrix defects in diseases such as glomerulopathy and fibrotic conditions.The article reviews the assembly of fibronectin (FN) into a fibrillar extracellular matrix (ECM) in multicellular organisms. FN, a ubiquitous ECM glycoprotein, is essential for tissue organization and development. The assembly process involves multivalent interactions between FN dimers and other ECM proteins, initiated by binding to cell surface receptors like α5β1 integrin. Receptor binding triggers FN self-association through the N-terminal assembly domain and promotes actin cytoskeleton organization to enhance cell contractility. Conformational changes in FN expose additional binding sites, facilitating fibril formation and conversion to a stable, insoluble form. The assembled FN matrix impacts tissue organization by contributing to the assembly of other ECM proteins. The review highlights key steps, molecular interactions, and cellular mechanisms involved in FN matrix assembly, emphasizing the importance of integrin binding, conformational changes, and the role of FN in the assembly of other ECM components like type I collagen, microfibrils, and elastic fibers. It also discusses the implications of FN matrix defects in diseases such as glomerulopathy and fibrotic conditions.