Plvap, or plasmalemma vesicle-associated protein, is a key endothelial cell-specific protein. It forms diaphragms in endothelial microdomains like caveolae, fenestrae, and transendothelial channels, regulating nutrient exchange, leukocyte migration, and vascular permeability. It is considered a major factor influencing endothelial cell permeability and thus vascular permeability [1].

Loss of Plvap in knockout mice leads to premature mortality due to disrupted homeostasis, highlighting its importance in maintaining normal physiological states [1]. In diseases such as cancer, traumatic spinal cord injury, and acute ischemic brain disease, Plvap is upregulated, accompanied by pro-angiogenic or pro-inflammatory responses [1]. In liver cirrhosis, ACKR1+ and PLVAP+ endothelial cells expand, enhancing leucocyte transmigration [2]. In hepatocellular carcinoma, fetal-like reprogramming involves re-emergence of PLVAP/VEGFR2 endothelial cells [3]. In chronic liver disease, the senescent secretome drives PLVAP expression in hepatic endothelial cells, promoting monocyte transmigration [4]. In stomach adenocarcinoma, high PLVAP expression is associated with poor prognosis [5]. In diabetic kidney disease, PLVAP is an early marker of glomerular endothelial injury [6]. In heart development, it is expressed in various heart-related cell types, and its expression changes in cardiac hypertrophy and failure models [7]. Mutations in PLVAP are associated with protein-losing enteropathy [8], and in the context of the blood-brain barrier, loss of Unc5B leads to increased PLVAP expression and BBB leak [9].

In conclusion, Plvap plays a crucial role in maintaining vascular homeostasis and is involved in multiple disease-related processes. Gene knockout mouse models have been instrumental in revealing its essential functions, such as its role in preventing premature mortality. Its association with various diseases including cancer, liver cirrhosis, and kidney disease emphasizes its potential as a therapeutic target.