Cell-adhesion molecules, once believed to function primarily in tethering cells to extracellular ligands, are now recognized as having broader functions in cellular signalling cascades. The CD44 transmembrane glycoprotein family adds new aspects to these roles by participating in signal-transduction processes — not only by establishing specific transmembrane complexes, but also by organizing signalling cascades through association with the actin cytoskeleton. CD44 and its associated partner proteins monitor changes in the extracellular matrix that influence cell growth, survival and differentiation.