Lck, or lymphocyte-specific protein tyrosine kinase, is a Src-related non-receptor protein tyrosine kinase. It is essential for T-cell development, activation, and homeostasis, and plays a crucial role in the T-cell antigen receptor (TCR) signaling pathway. By phosphorylating TCR-associated CD3 chains and downstream molecules, it initiates and propagates TCR signaling. Lck is also involved in other cellular processes such as cell cycle control, adhesion, motility, proliferation, and differentiation [1,2,3].

Studies using Lck knock-out (KO) mice or Lck-deficient T-cell lines have shown that Lck is critical for the initiation of TCR signaling. In LCKFREE mice, where endogenous Lck is mutated and unable to bind co-receptors, the TCR repertoire of influenza A virus-derived pMHC-specific CD8 and CD4 T cells is significantly narrowed, and CD4-fated T cells are redirected to the CD8 lineage, indicating that LCK-co-receptor association is crucial for T-cell lineage fidelity and maximizing antigen-specific T-cell repertoire diversity [4]. In addition, complete LCK deficiency in humans, as seen in some cases, leads to profound T-cell immune deficiency, reduced CD4 and CD8 surface expression, and characteristic TCR signaling disorders [1].

In conclusion, Lck is a key regulator in T-cell-related biological processes. Model-based research, especially KO mouse models, has revealed its significance in maintaining T-cell function and lineage integrity. Understanding Lck's role has implications for treating T-cell-related immune deficiencies and hematological malignancies [1,2,5].