Extracellular matrix proteins play important roles in many different biological processes. Our recent work has discovere important roles for the ECM protein mindin in both innate and adaptive immune responses. Mindin is a member of the F-spondin family of extracellular matrix proteins, which are classified by the presence of an FSI/FS2 domain and one or more thrombospondin type 1 (TSR) repeats. Madin is highly conserved throughout evolution and is broadly expressed in several organs including central and peripheral lymphoid tissues. As a component of the extracellular matrix, mindin exerts several important functions in immune responses. Mindin functions as a pattern recognition molecule for microbial pathogen recognition and is required for effective macrophage activation as well as phagocytosis of microbes. In addition, it promotes leukocyte trafficking during inflammatio in vivo. Mindin is also essential for the adaptive immune response by inducing small GTPase expression in dendritic cells which is required for efficient T cell priming. These effects are largely mediated through the interaction of mindin with multiple cell surface integrins, which likely results in integrin clustering and the induction of downstream signaling cascades. The focus of this review is to highlight these recent discoveries that demonstrate the necessary roles for mindin during innate and adaptive immunity. © 2007 Bentham Science Publishers Ltd.