The article discusses the role of REST (RE1-silencing transcription factor) in adult neurons, focusing on its physiological and pathological functions. REST is a zinc-finger transcription factor that represses the expression of thousands of genes, many of which are neuron-specific. In adult neurons, REST levels are low and govern the expression of specific neuronal phenotypes, including transcription factors, transmitter release proteins, voltage-dependent and receptor channels, and signaling proteins. REST also influences miRNA expression and mRNA splicing, contributing to neuronal specificity. In healthy aging humans, REST levels increase in hippocampal and cortical neurons, potentially due to increased stress and Wnt signaling, leading to the upregulation of protective genes and downregulation of potentially toxic genes. However, in Alzheimer's disease, REST levels remain in the cytoplasm, accumulating within autophagosomes, which may contribute to neuronal degeneration. REST is involved in several brain diseases, including schizophrenia, X-linked mental retardation, Down syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, and epilepsy. In these conditions, REST plays a role in gene regulation, miRNA expression, and epigenetic changes, contributing to neuronal dysfunction and disease progression. The article also discusses therapeutic approaches targeting REST, such as drugs that inhibit histone deacetylases or interfere with REST binding to target genes, which could be used to treat various brain disorders. Overall, REST is a critical factor in the physiology and pathology of adult neurons, and its complex actions make it a promising target for therapeutic interventions.The article discusses the role of REST (RE1-silencing transcription factor) in adult neurons, focusing on its physiological and pathological functions. REST is a zinc-finger transcription factor that represses the expression of thousands of genes, many of which are neuron-specific. In adult neurons, REST levels are low and govern the expression of specific neuronal phenotypes, including transcription factors, transmitter release proteins, voltage-dependent and receptor channels, and signaling proteins. REST also influences miRNA expression and mRNA splicing, contributing to neuronal specificity. In healthy aging humans, REST levels increase in hippocampal and cortical neurons, potentially due to increased stress and Wnt signaling, leading to the upregulation of protective genes and downregulation of potentially toxic genes. However, in Alzheimer's disease, REST levels remain in the cytoplasm, accumulating within autophagosomes, which may contribute to neuronal degeneration. REST is involved in several brain diseases, including schizophrenia, X-linked mental retardation, Down syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, and epilepsy. In these conditions, REST plays a role in gene regulation, miRNA expression, and epigenetic changes, contributing to neuronal dysfunction and disease progression. The article also discusses therapeutic approaches targeting REST, such as drugs that inhibit histone deacetylases or interfere with REST binding to target genes, which could be used to treat various brain disorders. Overall, REST is a critical factor in the physiology and pathology of adult neurons, and its complex actions make it a promising target for therapeutic interventions.