EGFL8 (EGF-like domain multiple 8) is a secreted protein containing two EGF-like domains and a calcium-binding domain, with a molecular mass of 32 kDa 1. The protein is widely expressed across diverse tissues including lymphoid organs, reproductive tissues, and gastrointestinal organs 1. During vascular development, EGFL8 serves as a marker gene for arterial endothelial cells (aECs) in embryonic vasculogenesis 2. It is preferentially expressed in cerebral arterioles and arteries 3, and acts as a direct substrate of the serine protease HTRA1 3. In pathological contexts, EGFL8 functions as a tumor suppressor: its downregulation promotes cancer progression in ovarian and gastric cancers through ERK/MAPK signaling activation, correlating with increased proliferation, EMT markers, and poor prognosis 4 5. In diabetic retinopathy, the long noncoding RNA PPT2-EGFL8 acts as a competing endogenous RNA, buffering miR-423-5p to inhibit pathological neovascularization 6. Additionally, EGFL8 accumulates in Alzheimer's disease brains, particularly in amyloid-beta plaques in the hippocampus and occipital cortex, suggesting roles in amyloidosis-associated pathology 7. These findings establish EGFL8 as a vascular development regulator with protective functions against cancer progression and neurovascular disease.