The blood-brain barrier (BBB) is a specialized system of brain microvascular endothelial cells (BMVEC) that protects the brain from toxins, supplies nutrients, and filters harmful substances. It functions in conjunction with other components of the neurovascular unit, including astrocytes, pericytes, neurons, and the basement membrane, to maintain CNS function. Transport across the BBB is restricted by physical (tight junctions) and metabolic barriers. The BBB's functional polarity between luminal and abluminal surfaces limits drug delivery to the CNS. BBB dysfunction contributes to many CNS diseases, such as Alzheimer's, Parkinson's, and multiple sclerosis. Common intracellular pathways regulate BBB integrity, and understanding tight junctions and transport systems can lead to therapies for BBB dysfunction. The BBB is composed of a microvascular endothelium, astrocytes, basement membrane, and pericytes, forming the neurovascular unit. BMVEC have unique structural components, including tight junctions (TJ), adherent junctions (AJ), and junctional adhesion molecules (JAM), which contribute to their barrier function. BMVEC have a uniform cytoplasm with few pinocytotic vesicles and lack fenestrations. They contain more mitochondria than other endothelial cells, enhancing nutrient transport. Enzymatic barriers, such as γ-glutamyl transpeptidase and alkaline phosphatase, metabolize drugs and nutrients. The BBB has a functional polarity, with enzymes and transporters distributed differently on the luminal and abluminal surfaces. Astrocytes envelop most of the BBB endothelium and interact with BMVEC to regulate BBB development and function. In vitro studies show that astrocyte coculture with BMVEC maintains BBB tightness. Astrocyte loss can impair BBB integrity, but it can be restored. Pericytes are contractile cells that associate with endothelial cells and may influence BBB structure. Pericytes can mimic astrocyte effects on BBB tightness. Neurons regulate microcirculation due to their high metabolic demands. The BBB's structural and functional integrity is crucial for CNS health, and understanding its regulation is essential for developing therapies for BBB-related diseases.The blood-brain barrier (BBB) is a specialized system of brain microvascular endothelial cells (BMVEC) that protects the brain from toxins, supplies nutrients, and filters harmful substances. It functions in conjunction with other components of the neurovascular unit, including astrocytes, pericytes, neurons, and the basement membrane, to maintain CNS function. Transport across the BBB is restricted by physical (tight junctions) and metabolic barriers. The BBB's functional polarity between luminal and abluminal surfaces limits drug delivery to the CNS. BBB dysfunction contributes to many CNS diseases, such as Alzheimer's, Parkinson's, and multiple sclerosis. Common intracellular pathways regulate BBB integrity, and understanding tight junctions and transport systems can lead to therapies for BBB dysfunction. The BBB is composed of a microvascular endothelium, astrocytes, basement membrane, and pericytes, forming the neurovascular unit. BMVEC have unique structural components, including tight junctions (TJ), adherent junctions (AJ), and junctional adhesion molecules (JAM), which contribute to their barrier function. BMVEC have a uniform cytoplasm with few pinocytotic vesicles and lack fenestrations. They contain more mitochondria than other endothelial cells, enhancing nutrient transport. Enzymatic barriers, such as γ-glutamyl transpeptidase and alkaline phosphatase, metabolize drugs and nutrients. The BBB has a functional polarity, with enzymes and transporters distributed differently on the luminal and abluminal surfaces. Astrocytes envelop most of the BBB endothelium and interact with BMVEC to regulate BBB development and function. In vitro studies show that astrocyte coculture with BMVEC maintains BBB tightness. Astrocyte loss can impair BBB integrity, but it can be restored. Pericytes are contractile cells that associate with endothelial cells and may influence BBB structure. Pericytes can mimic astrocyte effects on BBB tightness. Neurons regulate microcirculation due to their high metabolic demands. The BBB's structural and functional integrity is crucial for CNS health, and understanding its regulation is essential for developing therapies for BBB-related diseases.