Wiskott-Aldrich syndrome protein (WASP) (WASP)

The Wiskott-Aldrich syndrome protein (WASP) is a key cytoplasmic regulator of the actin cytoskeleton, expressed exclusively in hematopoietic cells. It serves as an actin nucleation-promoting factor that, upon activation by Rho-family GTPases like CDC42, stimulates the Arp2/3 complex to initiate the formation of branched actin filaments. This process is critical for essential cellular activities, including the formation of the immunological synapse between T cells and antigen-presenting cells, cell migration, and platelet production and function. Deficiency or dysfunction of WASP, caused by mutations in the WAS gene, leads to Wiskott-Aldrich syndrome, a primary immunodeficiency characterized by microthrombocytopenia, eczema, and increased susceptibility to infections, autoimmunity, and malignancies. Historically, the primary curative treatment has been allogeneic hematopoietic stem cell transplantation. However, WASP has become a major target for gene therapy, where autologous hematopoietic stem cells are modified ex vivo with lentiviral vectors to restore functional WASP expression. Therapeutic success in these cases is measured by the reconstitution of immune function and stabilization of platelet counts.

Other names

WAS proteinWASIMD2THCTHC1SCNXWASPA

Gene replacement therapy (lentiviral vector-mediated delivery of human WAS cDNA to restore WASP expression and function)