Zap70, short for zeta-chain associated protein kinase 70 kDa, is a nonreceptor tyrosine kinase. It plays essential roles in initiating T-cell receptor (TCR) signaling in T-lymphocytes, being at the crossroads of several signaling pathways that control T lymphocyte development and function [2]. It is also involved in B-cell receptor (BCR) signaling in certain B-cell malignancies. The PI3K-pathway is one of the associated pathways, and its normal developmental separation from SYK is crucial as a safeguard [1].

Mouse models have revealed that partial defects in Zap70 activity can be associated with autoimmunity, suggesting its involvement in the balance between immunity and tolerance [2]. In B-cell chronic lymphocytic leukemia (CLL), aberrant co-expression of Zap70 with SYK is considered a biomarker of aggressive disease and poor clinical outcomes. Mouse models may help further understand how this aberrant expression functions as an oncogenic driver in CLL and other B-cell malignancies [1].

In conclusion, Zap70 is a key regulator in adaptive immunity, with its function being essential for normal T-cell development and function. Its abnormal expression is linked to diseases like autoimmunity and B-cell malignancies. Studies using mouse models have been instrumental in uncovering its role in maintaining the balance between immunity and tolerance and in understanding disease-associated mechanisms.