CD80 is a transmembrane B7-family costimulatory molecule that plays a central role in T cell activation and immune regulation. CD80 primarily functions as a ligand for CD28 and CTLA-4 receptors on T cells, promoting CD28-mediated costimulation while being subject to regulation by CTLA-4 1. S-palmitoylation of CD80 at multiple cysteine residues by the palmitoyl-transferase zDHHC20 is essential for its stability, membrane localization, and costimulatory function 2. Beyond classical costimulation, CD80 on antigen-presenting cells interacts with PD-L1 in cis, disrupting PD-L1/PD-1 binding and limiting inhibitory signals during T cell activation 3. CD80 expression extends beyond professional APCs; activated CD4+ T cells express CD80 in a CD28-dependent manner, and CD80+ T cells display regulatory T cell characteristics including FoxP3 expression and reduced proliferation 4. Clinically, CD80 dysregulation contributes to multiple pathologies: allergens and irritants upregulate CD80 in keratinocytes during contact dermatitis 5, and CD80/86 elevation associates with increased mortality in sepsis 6. In cancer immunotherapy, CD86 but not CD80 blockade enhances anti-tumor immunity when combined with radiotherapy and PD-1 inhibition 7.