VEGFC (vascular endothelial growth factor C) is a growth factor primarily functioning in lymphangiogenesis—the formation of new lymphatic vessels from pre-existing ones 1. VEGFC acts as a key lymphangiogenic stimulator by binding and activating VEGFR3 expressed on lymphendothelial cells 1. Beyond lymphatic vessel development during embryogenesis and maintenance in adults, VEGFC also promotes angiogenesis and affects vascular permeability, with emerging evidence supporting its role in glomerular endothelial barrier function 2. Mechanistically, VEGFC secretion is regulated through multiple pathways in cancer contexts. In bladder cancer, the UBE2C-SNAT2 axis promotes VEGFC secretion via glutamine metabolism to drive lymphangiogenesis 3. In cervical cancer, cholesterol reprogramming via DHCR7 upregulates VEGFC secretion through the KANK4/PI3K/AKT pathway 4. Cancer-associated fibroblasts stimulated by PDGF-D secrete elevated VEGFC levels, promoting tumor lymphatic expansion 5. The lncRNA MIR503HG suppresses VEGFC via NOTCH1 signaling in renal cell carcinoma 6. Clinically, VEGFC overexpression correlates with poor prognosis in cutaneous squamous cell carcinoma, associating with tumor progression and reduced disease-free survival 7. VEGFC polymorphisms associate with autoimmune thyroiditis susceptibility 8. Conversely, podocyte-directed VEGFC gene therapy shows therapeutic promise in diabetic kidney disease by protecting glomerular permeability and glycocalyx integrity 2.