PECAM-1 is a cell-cell adhesion molecule primarily expressed on platelets and endothelial cells that functions as a key mediator of vascular homeostasis and endothelial junction integrity 1. The protein operates through homophilic interactions and serves as a component of a mechanosensory complex at endothelial cell-cell junctions, including interactions with VE-cadherin, VEGF receptors, and Plexin D1 1. PECAM-1 is activated downstream of latrophilin-2-mediated G protein signaling in response to fluid shear stress from blood flow, triggering cascades essential for vascular development and arterial remodeling 1. The molecule is upregulated during inflammatory responses, as observed in Fabry disease where complement activation increases PECAM-1 expression on endothelial cells and leukocytes, promoting excessive leukocyte recruitment 2. Therapeutically, antibody-directed targeting of PECAM-1 enables enhanced delivery of mRNA-based therapeutics to the lungs, achieving approximately 200-fold increased pulmonary mRNA delivery compared to non-targeted approaches 3. PECAM-1 expression is clinically relevant as a marker of endothelial dysfunction in atherosclerosis and NAFLD-associated cardiovascular disease 4. The gene localizes to chromosome 17 5.