ICOS (inducible T cell costimulator) is a stimulatory receptor expressed on activated T cells that delivers critical costimulatory signals upon binding to its ligand ICOSL on antigen-presenting cells 1. ICOS engagement enhances T cell proliferation, lymphokine secretion including IL-10, cell-cell adhesion molecules, and B cell antibody responses 2. Mechanistically, ICOS potentiates TCR-induced calcium flux through PLCG1 and actin remodeling, while independently activating PI3K signaling 3. ICOS is essential for T follicular helper cell differentiation and T regulatory cell development, with an ICOS-c-Maf-IL-7 axis pivotal to tissue-resident CD8+ T cell commitment in skin 4. ICOS expression is dynamically regulated post-transcriptionally by multiple RNA-binding proteins including Roquin-1/2, Celf1, and Igf2bp3 5. Clinically, ICOS holds dual significance: in cancer immunotherapy, ICOS-expressing CD4+ T cells identify tumor-reactive infiltrating lymphocytes with oligoclonal T cell receptor repertoires 6, and ICOS-ICOSL pathway targeting enhances antitumor responses in combination checkpoint blockade strategies 7. However, IL-2-mediated ICOS upregulation on tumor-resident Tregs during PD-1 blockade can paradoxically promote immunosuppression, suggesting ICOS inhibition may improve checkpoint immunotherapy efficacy 8. ICOS mutations associate with common variable immunodeficiency.