The process of metastasis is complex consisting of a series of sequential steps. Initially, tumor cells detach from the primary tumor, migrate through the surrounding tissue and eventually invade the lymphatic system or blood vessels. As a next step, circulating tumor cells temporarily adhere to endothelial cells and then extravasate by infiltrating the underlying basement membrane. Finally, cells migrate to a suitable location where they proliferate and form metastases (Nicolson, 1988; Stetler-Stevenson et al., 1993; Engers and Gabbert, 2000; Orr et al., 2000). Accordingly, the capacity of tumor cells to form metastatic foci correlates with the ability to proteolytically degrade basement membrane barriers and to adhere to and migrate through extracellular matrix layers (StetlerStevenson et al., 1993; Engers and Gabbert, 2000). Modulation of the actin cytoskeleton is critical for tumor cell migration and invasion (Ridley et al., 2003). Therefore, actin-binding proteins which regulate this modulation may be valuable targets to inhibit the invasive properties of tumor cells and, hence, reduce metastasis. Changes in the actin cytoskeleton are accomplished by a variety of actin-binding proteins such as cofilin, a-actinin, filamin, fascin and the plastins (Ridley et al., 2003; Samstag et al., 2003). Interestingly, the hematopoetic isoform of the plastins, L-plastin, is not only expressed by hematopoetic cells, but also by most human cancer cell lines (Lin et al., 1993a; Park et al., 1994). Here, we describe the current knowledge about the expression and function of L-plastin in human cancer cells and its implications for the therapy of cancer. ARTICLE IN PRESS