ESM1 (endothelial cell-specific molecule 1) is a secreted proteoglycan primarily functioning in angiogenesis and vascular biology. The protein promotes angiogenic sprouting and endothelial cell function, with expression as a structural component of islet-specific endothelial cells in pancreatic vasculature 1. ESM1 acts as a paracrine signaling molecule that activates PDGFRA on target cells, enhancing proliferation and angiogenic properties through Myc upregulation 2. In cancer pathophysiology, ESM1 drives metabolic reprogramming and epithelial-to-mesenchymal transition across multiple tumor types. In ovarian cancer, hypoxia-induced ESM1 facilitates the PKM2-dependent Warburg effect and vascular mimicry through PKM2 SUMOylation and STAT3 phosphorylation 3, while also regulating lipid metabolism via an IGF2BP3/KLF10/BECN1 feedback loop 4. In gastric cancer, ESM1 triggers EMT by enhancing EGFR/HER3-Akt/ANGPT2 signaling 5. ESM1 is upregulated across cancer types and associates with poor prognosis and increased metastatic potential 6. Beyond cancer, ESM1 expression is disrupted in diabetes, suggesting broader pathophysiological roles in metabolic disease 1. These findings identify ESM1 as a potential therapeutic target for cancer and metabolic disorders.