NAD(P)H Quinone Dehydrogenase 1 (NQO1) plays a crucial role in the central nervous system (CNS) by regulating neuronal function, synaptic plasticity, cellular adaptation to oxidative stress, neuroinflammation, and degenerative processes. Impairment of NQO1 activity can lead to abnormal neurotransmitter release, increased oxidative stress, and cellular injury, affecting neural circuit function and synaptic transmission. Abnormalities in NQO1 enzyme activity are linked to multiple neurological disorders, including Parkinson's disease, Alzheimer's disease, epilepsy, multiple sclerosis, cerebrovascular disease, traumatic brain injury, and brain malignancy. NQO1 also contributes to various aspects of tumorigenesis and treatment response in brain tumors. The study reviews the current understanding of NQO1 dysregulations in neurological disorders, emphasizing its potential as a biomarker and therapeutic target. The review covers the structure, functions, polymorphisms, and regulatory pathways of NQO1, as well as its involvement in specific neurological disorders such as Alzheimer's, Parkinson's, multiple sclerosis, and cerebrovascular diseases. The discussion highlights the therapeutic potential of targeting NQO1 for diagnostic, preventive, and therapeutic approaches in neurological disorders.NAD(P)H Quinone Dehydrogenase 1 (NQO1) plays a crucial role in the central nervous system (CNS) by regulating neuronal function, synaptic plasticity, cellular adaptation to oxidative stress, neuroinflammation, and degenerative processes. Impairment of NQO1 activity can lead to abnormal neurotransmitter release, increased oxidative stress, and cellular injury, affecting neural circuit function and synaptic transmission. Abnormalities in NQO1 enzyme activity are linked to multiple neurological disorders, including Parkinson's disease, Alzheimer's disease, epilepsy, multiple sclerosis, cerebrovascular disease, traumatic brain injury, and brain malignancy. NQO1 also contributes to various aspects of tumorigenesis and treatment response in brain tumors. The study reviews the current understanding of NQO1 dysregulations in neurological disorders, emphasizing its potential as a biomarker and therapeutic target. The review covers the structure, functions, polymorphisms, and regulatory pathways of NQO1, as well as its involvement in specific neurological disorders such as Alzheimer's, Parkinson's, multiple sclerosis, and cerebrovascular diseases. The discussion highlights the therapeutic potential of targeting NQO1 for diagnostic, preventive, and therapeutic approaches in neurological disorders.