ZAP70 (zeta-chain (TCR) associated protein kinase 70kD), expressed primarily in T and NK cells, is a Syk family cytosolic protein tyrosine kinase that consists of two N-terminal SH2 domains and a C-terminal tyrosine kinase domain. Upon T cell receptor activation and phosphorylation of TCR ITAMs by Src family kinases, ZAP70 is recruited to phosphorylated ITAM sequences and subsequently phosphorylated on several tyrosine residues. ZAP70 has been implicated in several immune disorders. An autosomal recessive form of SCID in humans has been attributed to a homozygous mutation in the kinase domain of ZAP70. ZAP70 expression also defines an aggressive subset of CLL.