The latter, together with the phenotypic overlap between DEF6 deficiency and LRBA deficiency or CTLA-4 insufficiency and the reported therapeutic efficacy of CTLA-4-Ig therapy (abatacept) in treating autoimmunity, suggest that a loss of proper trafficking of CTLA-4 is a major mechanism of immune dysregulation in DEF6 deficiency. The gene discussed is CTLA4; the disease is Autoimmunity.