The ZAP7 (ζ-associated protein of 7 kDa) is expressed in the aggressive form of B-cell chronic lymphocytic leukemia (CLL). ZAP7 plays a critical role for ZAP7 in chemokine-mediated, inside-out signaling to integrins in trisomy. The phosphorylation of ZAP7 activated the downstream NF-κB signaling pathway, which is involved in both T cell growth and function. On the other hand, the expression of Zap7 in B-cell malignancies correlates with the severity of the disease. Because of its role in immune-related disorders, Zap7 has become a therapeutic target for the treatment of human diseases.