The blood-brain barrier (BBB) is a specialized multicellular structure that maintains brain homeostasis by regulating the passage of molecules, ions, and immune cells between the blood and the central nervous system (CNS). It is composed of endothelial cells (ECs), astrocytes, pericytes, and the extracellular matrix (ECM), forming the neurovascular unit (NVU). The BBB's unique properties, such as tight junctions (TJs), low transcytosis, and limited immune cell infiltration, are essential for protecting the brain from toxins and pathogens. BBB development and maintenance involve complex interactions between ECs and other cell types, including pericytes and astrocytes, which provide structural and functional support. Key signaling pathways, such as Wnt, VEGF, and SHH, play critical roles in BBB formation and maturation. Disruption of the BBB can lead to neuroinflammation, neurodegeneration, and neurological diseases. Recent studies have highlighted the importance of TJ proteins, such as claudin-5 and occludin, in maintaining BBB integrity. BBB dysfunction is associated with various neurological disorders, including stroke, epilepsy, and amyotrophic lateral sclerosis (ALS). In stroke, oxidative stress and MMP activity contribute to BBB breakdown, leading to increased vascular permeability and immune cell infiltration. In epilepsy, BBB disruption can lead to ion and neurotransmitter imbalances, causing abnormal neuronal activity. In ALS, BBB breakdown is linked to neuroinflammation and motor neuron degeneration. Neuromyelitis optica (NMO) is an autoimmune disease where AQP4-IgG autoantibodies target the BBB, leading to BBB disruption and astrocyte damage. Strategies for BBB repair include glucocorticosteroid treatment, which can restore BBB integrity by modulating TJ proteins and inflammatory responses. Mesenchymal stromal cells (MSCs) are being investigated as a potential therapeutic approach for BBB repair. Advances in BBB research, including the development of in vitro models and in silico approaches, are providing new insights into BBB function and dysfunction. Understanding the mechanisms of BBB development, maintenance, and disruption is crucial for developing effective therapies for neurological diseases.The blood-brain barrier (BBB) is a specialized multicellular structure that maintains brain homeostasis by regulating the passage of molecules, ions, and immune cells between the blood and the central nervous system (CNS). It is composed of endothelial cells (ECs), astrocytes, pericytes, and the extracellular matrix (ECM), forming the neurovascular unit (NVU). The BBB's unique properties, such as tight junctions (TJs), low transcytosis, and limited immune cell infiltration, are essential for protecting the brain from toxins and pathogens. BBB development and maintenance involve complex interactions between ECs and other cell types, including pericytes and astrocytes, which provide structural and functional support. Key signaling pathways, such as Wnt, VEGF, and SHH, play critical roles in BBB formation and maturation. Disruption of the BBB can lead to neuroinflammation, neurodegeneration, and neurological diseases. Recent studies have highlighted the importance of TJ proteins, such as claudin-5 and occludin, in maintaining BBB integrity. BBB dysfunction is associated with various neurological disorders, including stroke, epilepsy, and amyotrophic lateral sclerosis (ALS). In stroke, oxidative stress and MMP activity contribute to BBB breakdown, leading to increased vascular permeability and immune cell infiltration. In epilepsy, BBB disruption can lead to ion and neurotransmitter imbalances, causing abnormal neuronal activity. In ALS, BBB breakdown is linked to neuroinflammation and motor neuron degeneration. Neuromyelitis optica (NMO) is an autoimmune disease where AQP4-IgG autoantibodies target the BBB, leading to BBB disruption and astrocyte damage. Strategies for BBB repair include glucocorticosteroid treatment, which can restore BBB integrity by modulating TJ proteins and inflammatory responses. Mesenchymal stromal cells (MSCs) are being investigated as a potential therapeutic approach for BBB repair. Advances in BBB research, including the development of in vitro models and in silico approaches, are providing new insights into BBB function and dysfunction. Understanding the mechanisms of BBB development, maintenance, and disruption is crucial for developing effective therapies for neurological diseases.