Panel A: Diagram of LCK regulation showing bound and free states cycling among active, primed, and inactive conformations. CD45 dephosphorylates Y505 to promote activation, while CSK phosphorylates Y505 to maintain the inactive state. Autophosphorylation of Y394 stabilizes the active conformation. Zn2 positive coordinates LCK binding to CD4/CD8 co-receptors. Panel B: Diagram of TCR signaling upon engagement. Free, active LCK initiates signaling by phosphorylating ITAMs within CD3 chains. Co-receptor-bound LCK modulates sensitivity and efficiency. ITAM phosphorylation enables ZAP-70 recruitment and activation of downstream effectors, including LAT, SLP-76, and ITK.