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Studies of these <jats:styled-content style=\"fixed-case\">PID<\/jats:styled-content>s have revealed a pivotal role for the actin cytoskeleton in almost all stages of immune system function, from hematopoiesis and immune cell development, through to recruitment, migration, intercellular and intracellular signaling, and activation of both innate and adaptive immune responses. The major focus of this review is the immune defects that result from mutations in the <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>iskott\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>ldrich syndrome gene (<jats:italic><jats:styled-content style=\"fixed-case\">WAS<\/jats:styled-content><\/jats:italic>), which have a broad impact on many different processes and give rise to clinically heterogeneous immunodeficiencies. 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