Non-Integrin Laminin Receptors: Shedding New Light and Clarity on Their Involvement in Human Diseases

The extracellular matrix (ECM) is a dynamic network of macromolecules that provides structural support for cells and orchestrates cell signaling, functions, and morphology. The basement membrane constitutes a peculiar sheet-like type of ECM located between epithelial tissues and underlying connective tissues. The major constituent of the basement membrane is laminin, which exerts a remarkable repertoire of biological functions such as cell differentiation, migration, adhesion, and wound healing. Laminin performs its functions by interacting with two main classes of receptors, the integrin and the non-integrin laminin receptors, creating a complex network essential for tissue integrity and regeneration. Dysfunctional actions of laminin are the cause of diverse human diseases, including cancer, infectious, and neurodegenerative diseases. This topic has attracted researchers for some time, but the diversity of cell-surface receptors, through which laminin signaling occurs, makes the role of laminin controversial. Moreover, different laminin isoforms were identified, and each specific tissue basement membrane differs from the others in their laminin composition. This review focuses on the structural and molecular basis and pathophysiological relevance of specific interactions between laminins and non-integrin receptors in development, health, and disease.