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Cells deficient in the Wiskott\u2013Aldrich syndrome protein (WASP) have been used to demonstrate the importance of the dynamic remodelling of the actin\u2010based cytoskeleton during the selective adhesion and migration of these cells. Unlike most cell types, macrophages, dendritic cells, and osteoclasts utilize a specialized adhesive array termed the podosome in order to migrate. Podosomes are composed of many of the same structural and regulatory proteins as seen in the more commonly found focal adhesion, but are unique in their requirement for WASP. Without WASP, podosomes cannot form and the affected cells are obliged to use focal adhesions for their migratory activities. Once activated by a series of upstream regulatory proteins, WASP acts as a scaffold for the binding of the potent actin nucleating protein complex known as Arp2\/3. This article reviews the available evidence that suggests that failures in the regulation of the actin cytoskeleton may contribute significantly to the immunopathology of the Wiskott\u2013Aldrich syndrome. Copyright \u00a9 2004 Pathological Society of Great Britain and Ireland. 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