CD69 is a type II transmembrane glycoprotein and a member of the C-type lectin superfamily. It is a classical early marker of lymphocyte activation, appearing rapidly on the cell surface after stimulation. Structurally, CD69 is a disulfide-linked homodimer protein with two differentially glycosylated subunits (28鈥?2 kDa), each consisting of an extracellular C-type lectin domain connected to a single-spanning transmembrane region followed by a short cytoplasmic tail. It is broadly expressed on the surfaces of most hematopoietic lineages, including activated T and B lymphocytes, natural killer (NK) cells, murine macrophages, neutrophils, and eosinophils, and is constitutively expressed on human monocytes, platelets, epidermal Langerhans cells, and bone-marrow myeloid precursors. CD69 plays various regulatory roles in immune responses, such as promoting tissue residency, regulating Th17/Treg cell differentiation, and contributing to the exhaustion of resident memory T cells, especially in the tumor microenvironment. Its ligands include galectin-1, calprotectin (S100A8/S100A9 complex), myosin light chains 9, 12a, and 12b (Myl9/12), and oxidized low-density lipoprotein (ox-LDL).