The term ‘matricellular’ has been applied to a group of extracellular proteins that do not contribute directly to the formation of structural elements in vertebrates but serve to modulate cell–matrix interactions and cell function. Our understanding of the mode of action of matricellular proteins has been advanced considerably by the recent elucidation of the phenotypes of mice that are deficient in these proteins. In many cases, aspects of these phenotypes have illuminated previously unsuspected consequences of the lack of appropriate interactions of cells with their environment.