TNFSF18 (TNF superfamily member 18) is a cytokine that binds to TNFRSF18/GITR and functions as a T-cell costimulator, lowering the threshold for T-cell activation and proliferation. It mediates NF-κB activation and increases phosphorylation of STAT1, upregulating adhesion molecules VCAM1 and ICAM1 to promote leukocyte adhesion to endothelial cells 1. TNFSF18 enhances CAR-T cell persistence and anti-tumor activity in solid tumors through increased IFN-γ, TNF-α, and IL-9 secretion, with higher proportions of central memory T cells and reduced exhaustion markers 2. Disease relevance is significant across multiple conditions. TNFSF18 is a genome-wide association study (GWAS)-identified risk locus for IgA nephropathy, a progressive kidney disease, enriched in inflammatory signaling pathways 3. In primary Sjögren syndrome, elevated GITRL (TNFSF18) correlates with disease activity and promotes pathogenic Th17 responses through a mTORC1-GM-CSF positive loop, with blockade showing therapeutic potential 4. TNFSF18 expression is upregulated in colorectal cancer and esophageal squamous cell carcinoma, associated with altered immune checkpoint expression 5 6, and identified as a potential therapeutic target in prostate cancer 7.