APOLD1 is a vascular-specific protein that functions as a critical regulator of endothelial cell barrier integrity and pathological angiogenesis. Primary function: APOLD1 modulates endothelial barrier permeability and is required for proper organization of endothelial cell-cell junctions and cytoskeleton 1. It also plays a role in secretory autophagy 1. Mechanism: APOLD1 is highly responsive to environmental factors including growth factor stimulation and hypoxia 2. It intrinsically controls endothelial cell proliferation, though not migration, and operates through membrane remodeling processes associated with inflammatory conditions 3. Disease relevance: While dispensable for developmental and postnatal angiogenesis, APOLD1 is essential for vascular recovery under pathological conditions such as ischemic stroke and arterial occlusion 2. APOLD1 deletion impairs tumor angiogenesis by reducing vessel perfusion 2. Clinical significance: APOLD1 represents a bleeding disorder gene and has been identified as a potential therapeutic target for metabolic dysfunction-associated steatotic liver disease 4. Its upregulation in tumor endothelium and involvement in gastroparesis pathophysiology indicate broader clinical relevance 5, 6.