Integrin-linked kinase (ILK*) is a multidomain focal adhesion protein that is critically involved in adhesion of cells to the extracellular matrix (ECM) and signal transduction. The figure shows the interactions involving ILK and other related proteins and the downstream signals these elicit. ILK interacts with the cytoplasmic domains of β integrins (eg β1 integrin). Furthermore, it binds with high affinity to PINCH, a focal adhesion protein comprising five LIM domains. The ILK-PINCH binding is mediated by the N-terminal ankyrin (ANK) repeat domain of ILK and the second Zn finger located within the N-terminal-most LIM domain (LIM1) of PINCH. ILK also interacts with CHILKBP, an actin-binding focal adhesion protein containing two calponinhomology (CH) domains. Human CHILKBP is structurally closely related to rat actopaxin, a paxillin-and actinbinding protein. In addition, ILK can bind to the paxillin LD1 motif. The interaction between ILK and CH-ILKBP is mediated by the C-terminal domain of ILK and the CH2 domain of CH-ILKBP. Simultaneous interactions mediated by the two separate (the N-and C-terminal) domains of ILK result in the formation of a stable PINCH–ILK–CH-ILKBP ternary complex in cells. The formation of this complex facilitates the localization of PINCH, ILK and CHILKBP to cell-ECM contact sites, at which they provide a crucial physical connection between transmembrane receptors such as integrins and the actin filaments. This function of the PINCH–ILK–CH-ILKBP complex is probably conserved in organisms ranging from nematodes and insects to humans.