EDIL3 is an extracellular matrix protein that promotes endothelial cell adhesion through αv/β3 integrin binding and regulates vascular morphogenesis 1. Beyond its canonical vascular role, EDIL3 functions as an endogenous inhibitor of neutrophil adhesion and plays a critical role in inflammatory regulation 1. In myocardial infarction, EDIL3 deficiency ameliorates adverse cardiac remodeling by enhancing neutrophil recruitment and neutrophil extracellular trap (NET)-mediated pro-inflammatory macrophage polarization, improving cardiac function and reducing fibrosis 1. EDIL3 is overexpressed in multiple cancers including pancreatic ductal adenocarcinoma and gastric cancer, where elevated expression correlates with poor prognosis, advanced TNM stage, and promotes anchorage-independent tumor growth through altered Bcl-2 family protein expression 2. Pan-cancer analysis reveals EDIL3 associates with extracellular matrix receptor interactions, focal adhesion pathways, immune infiltration, and immune checkpoints 3. In IgA nephropathy, EDIL3 is upregulated in mesangial cells and correlates with cell proliferation and matrix accumulation 4. The contrasting roles of EDIL3—protective in acute inflammation resolution but pro-tumorigenic in cancer—suggest context-dependent functions warranting further mechanistic investigation for therapeutic targeting.