DOCK8 is a guanine nucleotide exchange factor (GEF) that activates the small GTPase CDC42 by exchanging bound GDP for free GTP 1. During immune responses, DOCK8 functions critically in cell migration and cytotoxicity. It promotes CD4+ T cell migration in response to chemokine stimulation by locally activating CDC42 at the T cell leading edge membrane 2. DOCK8 also regulates NK cell cytotoxicity by controlling microtubule-organizing center polarization and lytic granule transport 3. DOCK8 deficiency causes autosomal recessive hyper-IgE syndrome, a combined immunodeficiency characterized by eczema, recurrent bacterial and viral skin infections, respiratory infections, and elevated serum IgE levels 4567. Recent findings reveal that DOCK8 deficiency involves both actin regulation defects and reduced regulatory T lymphocyte function in skin tissue, contributing to severe and persistent viral infections and inflammatory phenotype 7. The condition also increases susceptibility to giant condyloma acuminatum through compromised HPV immunity 8. Clinically, genetic diagnosis is essential for distinguishing DOCK8 deficiency from atopic dermatitis and other immunodeficiencies 6. Hematopoietic stem cell transplantation is the definitive curative treatment, significantly improving outcomes and abolishing most symptoms, though allergic manifestations may persist 57.