ZAP-70 (Zeta-chain-associated protein kinase 70) is a cytoplasmic protein tyrosine kinase that plays a crucial role in T cell receptor (TCR) signaling and is essential for T cell activation and development. It is primarily expressed in T cells, natural killer cells, and a subset of B cells. When the TCR binds to an antigen, the tyrosine kinase Lck is activated, phosphorylating the immunoreceptor tyrosine-based activation motifs (ITAMs) on the CD3 complex. These phosphorylated ITAMs serve as docking sites for ZAP-70, which is then activated and phosphorylates downstream molecules such as the linker for activation of T cells (LAT) and the SH2-domain-containing leukocyte protein of 76 kDa (SLP-76). This cascade of events leads to T cell activation, proliferation, and differentiation. In addition, ZAP-70 expression in B cells is associated with chronic lymphocytic leukemia (CLL), making it a potential biomarker and therapeutic target.