SVEP1 (Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1) is a large extracellular matrix protein with multifaceted roles in vascular biology and disease. The protein functions as an endogenous ligand for the orphan receptor PEAR1, promoting platelet activation through AKT/mTOR signaling pathways 1. SVEP1 plays critical roles in lymphatic vascular development, with knockout animals displaying severe edema and lymphatic system malformations 2. In vascular smooth muscle cells, SVEP1 promotes proliferation and migration, with EGR1 transcriptionally regulating its expression in response to oxidative stress 3. Disease-wise, SVEP1 demonstrates significant clinical relevance across multiple conditions. Mendelian randomization studies have established causal relationships between SVEP1 and cardiovascular disease, heart failure, and Alzheimer's disease 1 4 5. Genome-wide association studies have linked SVEP1 to primary open-angle glaucoma risk 6. Additionally, rare variants in SVEP1 have been identified in lymphedema patients, suggesting its potential role in lymphatic disorders 2. The protein's involvement in cancer biology includes regulation by cancer-associated fibroblasts, where it contributes to chemoresistance in bladder cancer 7. These diverse associations highlight SVEP1 as an important therapeutic target across multiple pathological conditions.