CD8α is a crucial immune glycoprotein that serves as a co-receptor for MHC class I peptide complexes, facilitating the connection between T cells and antigens presented by antigen-presenting cells （APCs）. It interacts with the T-cell receptor （TCR） and MHC class I molecules, recruits LCK kinase, and initiates multiple signaling pathways. CD8α can exist as either an α/β heterodimer or an α/α homodimer, with the αα homodimer being particularly abundant in intraepithelial lymphocytes （IELs） that protect mucosal surfaces. It is expressed on cytotoxic T cells （CTLs） and natural killer （NK） cells, playing a key role in cell-mediated immunity and the regulation of immune responses. Additionally, CD8α is involved in T cell activation and differentiation, and it is a biomarker for various diseases, including COVID-19 and certain cancers.