TNFSF14 (TNF superfamily member 14), also known as LIGHT, is a pleiotropic cytokine that functions as a costimulatory molecule in immunity and inflammation. TNFSF14 binds to TNFRSF14/HVEM on T cells to deliver costimulatory signals, promoting T cell proliferation and interferon-gamma production 1. The protein also interacts with other TNF receptor superfamily members including TNFRSF3 and TNFRSF6B, which modulate its immunological effects 2. Clinically, TNFSF14 dysregulation is implicated in multiple disease pathologies. In inflammatory bowel disease, activated mesenchymal populations expressing TNFSF14 emerge during colitis and impair epithelial proliferation, contributing to barrier dysfunction 3. Elevated TNFSF14 plasma levels correlate with COVID-19 severity 4. In cardiac pathology, TNFSF14/LIGHT promotes atrial fibrillation vulnerability and myocardial fibrosis through PI3Kγ/SGK1-dependent M2 macrophage polarization, with circulating TNFSF14 serving as a prognostic marker 5. Conversely, TNFSF14-TNFRSF14 interactions in reproductive immunity maintain decidual stromal cell homeostasis during pregnancy; dysregulation associates with spontaneous abortion 67. In hepatocellular carcinoma, TNFSF14-TNFRSF14 signaling drives immunotherapy resistance through Treg-CAF interactions; blocking this axis enhances anti-PD-1 efficacy 8. TNFSF14 expression also correlates with glioblastoma grade and prognosis, identifying it as an emerging immunotherapy target 9. Engineered TNFSF14 expression promotes tertiary lymphoid structure formation and antitumor immunity in colorectal cancer 10.