The blood–brain barrier (BBB) is a specialized system composed of brain microvascular endothelial cells (BMVEC), astrocytes, pericytes, and neurons, forming the neurovascular unit. Under physiological conditions, the BBB ensures the supply of nutrients to brain cells, filters harmful substances, and controls the entry of therapeutic agents into the central nervous system (CNS). The BBB's integrity is maintained through tight junctions, adherent junctions, and junctional adhesion molecules, as well as enzymatic barriers. Astrocytes, which envelop most of the BBB endothelium, play a crucial role in modulating the BBB's tightness and function. Pericytes, associated with the endothelium, regulate endothelial cell proliferation, survival, and migration, contributing to the BBB's structural integrity. Neurons, with their high metabolic demands, require tight regulation of the microcirculation to maintain proper brain function. Altered BBB function, often mediated by proinflammatory substances and disease-associated proteins, is a key factor in the pathogenesis of various CNS diseases, including Alzheimer's, Parkinson's, and multiple sclerosis. Understanding the regulation of tight junctions and transport systems can lead to the development of therapeutics to improve BBB function in health and disease.The blood–brain barrier (BBB) is a specialized system composed of brain microvascular endothelial cells (BMVEC), astrocytes, pericytes, and neurons, forming the neurovascular unit. Under physiological conditions, the BBB ensures the supply of nutrients to brain cells, filters harmful substances, and controls the entry of therapeutic agents into the central nervous system (CNS). The BBB's integrity is maintained through tight junctions, adherent junctions, and junctional adhesion molecules, as well as enzymatic barriers. Astrocytes, which envelop most of the BBB endothelium, play a crucial role in modulating the BBB's tightness and function. Pericytes, associated with the endothelium, regulate endothelial cell proliferation, survival, and migration, contributing to the BBB's structural integrity. Neurons, with their high metabolic demands, require tight regulation of the microcirculation to maintain proper brain function. Altered BBB function, often mediated by proinflammatory substances and disease-associated proteins, is a key factor in the pathogenesis of various CNS diseases, including Alzheimer's, Parkinson's, and multiple sclerosis. Understanding the regulation of tight junctions and transport systems can lead to the development of therapeutics to improve BBB function in health and disease.