Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders

Endocytic adaptor proteins are essential regulators of intracellular trafficking, coupling receptor internalization with downstream signaling. Recent discoveries have deepened our understanding of how endocytic adaptor proteins contribute to both physiological and pathological processes in the vascular system. This review summarizes the emerging roles of key adaptor proteins-such as epsins, disabled-2, and adaptor protein 2-across multiple vascular cell types, including endothelial cells, vascular smooth muscle cells, and macrophages. These adaptors have diverse but essential functions, ranging from regulating angiogenic signaling and maintaining endothelial barrier integrity to modulating inflammatory responses, vascular smooth muscle cells phenotypic switching, lipid uptake, and structural remodeling of blood vessels. We also highlight advances in therapeutic strategies, such as nanomedicine, viral expression vectors, DNA nanostructures, and small molecule inhibitors that target endocytic adaptors and their function. Understanding the diverse and cell-specific roles of endocytic adaptor proteins is important for gaining insights into vascular disease mechanisms and uncovering novel targets for therapeutic interventions.