E-selectin, also known as ELAM1 (Endothelial Leukocyte Adhesion Molecule-1), CD62E, or LECAM-2, is a key molecule in vascular pathophysiology, primarily regulating leukocyte adhesion and stable arrest to the endothelium in various inflammatory conditions. E-selectin is constitutively expressed in resting endothelial cells but becomes activated in response to inflammatory cytokines such as interleukin-1 (IL-1), bacterial lipopolysaccharide (LPS), viral infections, and tumor necrosis factor (TNF). The expression of E-selectin is regulated by transcription factors like NF-κB, ATF2, HMG I(Y), RUNX1, and ERG, which influence its activity and stability. E-selectin facilitates the interaction between circulating leukocytes and vascular endothelium, promoting leukocyte migration and inflammatory responses. It plays a crucial role in the homing of hematopoietic stem cells to the bone marrow niche and is involved in the recruitment of various immune cells to sites of inflammation. Soluble E-selectin (sE-selectin) serves as a biomarker for endothelial cell activation and is elevated in inflammatory diseases, including rheumatoid arthritis, psoriasis, atherosclerosis, and cancer. In diseases such as acute kidney injury (AKI), pulmonary injury, hepatic failure, and venous thromboembolism (VTE), E-selectin is upregulated due to oxidative stress, contributing to cellular damage, inflammation, and thrombosis. Therapeutic interventions targeting E-selectin, such as microRNAs, monoclonal antibodies, and drugs directly targeting E-selectin, have shown promise in reducing inflammation and improving outcomes in these conditions. The article reviews the molecular mechanisms of E-selectin expression, its ligands, and signaling pathways, as well as its role in various pathological conditions. It also discusses potential therapeutic targets and strategies for modulating E-selectin to address vascular diseases and inflammatory conditions.E-selectin, also known as ELAM1 (Endothelial Leukocyte Adhesion Molecule-1), CD62E, or LECAM-2, is a key molecule in vascular pathophysiology, primarily regulating leukocyte adhesion and stable arrest to the endothelium in various inflammatory conditions. E-selectin is constitutively expressed in resting endothelial cells but becomes activated in response to inflammatory cytokines such as interleukin-1 (IL-1), bacterial lipopolysaccharide (LPS), viral infections, and tumor necrosis factor (TNF). The expression of E-selectin is regulated by transcription factors like NF-κB, ATF2, HMG I(Y), RUNX1, and ERG, which influence its activity and stability. E-selectin facilitates the interaction between circulating leukocytes and vascular endothelium, promoting leukocyte migration and inflammatory responses. It plays a crucial role in the homing of hematopoietic stem cells to the bone marrow niche and is involved in the recruitment of various immune cells to sites of inflammation. Soluble E-selectin (sE-selectin) serves as a biomarker for endothelial cell activation and is elevated in inflammatory diseases, including rheumatoid arthritis, psoriasis, atherosclerosis, and cancer. In diseases such as acute kidney injury (AKI), pulmonary injury, hepatic failure, and venous thromboembolism (VTE), E-selectin is upregulated due to oxidative stress, contributing to cellular damage, inflammation, and thrombosis. Therapeutic interventions targeting E-selectin, such as microRNAs, monoclonal antibodies, and drugs directly targeting E-selectin, have shown promise in reducing inflammation and improving outcomes in these conditions. The article reviews the molecular mechanisms of E-selectin expression, its ligands, and signaling pathways, as well as its role in various pathological conditions. It also discusses potential therapeutic targets and strategies for modulating E-selectin to address vascular diseases and inflammatory conditions.