CD247 (CD3ζ) is a critical component of the T-cell receptor (TCR)-CD3 complex expressed on T lymphocytes and natural killer cells 1. It functions as a signal transduction molecule containing three immunoreceptor tyrosine-based activation motifs (ITAMs) in its cytoplasmic domain. Upon TCR engagement by antigen-presenting cells, CD247's ITAMs become phosphorylated by Src family kinases (LCK and FYN), creating docking sites for ZAP70 and initiating downstream signaling cascades essential for T-cell activation and adaptive immunity 2. CD247 is also involved in intrathymic T-cell differentiation and plays roles in activity-dependent synapse formation in retinal ganglion cells. CD247 dysfunction is clinically significant in multiple disease contexts. Homozygous null mutations cause immunodeficiency 25, while heterozygous nonsense mutations exert dominant-negative effects, reducing surface TCR expression and impairing T-cell signaling 2. CD247 deficiency is associated with systemic lupus erythematosus, with more than half of SLE patients showing attenuated or absent CD247 expression 3. Polymorphisms in CD247 are associated with type 1 diabetes, autoimmune thyroid disease 4, and rheumatoid arthritis 5. Additionally, CD247 expression levels serve as a potential biomarker for septic shock prognosis 6. Recent therapeutic applications exploit CD247's signaling properties in CAR-T cell engineering for cancer immunotherapy 7.