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The brain extracellular matrix (ECM) occupies the space between cells and is involved in cell–matrix and cell–cell adhesion. However, in addition to providing structural support to brain tissue, the ECM activates cell signaling and controls synaptic transmission. The expression and activity of brain ECM components are regulated by alcohol exposure. This review will discuss what is currently known about the effects of alcohol on the activity and expression of brain ECM components. An interpretation of how these changes might promote alcohol use disorder (AUD) will be also provided. Ethanol (EtOH) exposure decreases levels of structural proteins involved in the interstitial matrix and basement membrane, with a concomitant increase in proteolytic enzymes that degrade these components. In contrast, EtOH exposure generally increases perineuronal net components. Because the ECM has been shown to regulate both synaptic plasticity and behavioral responses to drugs of abuse, regulation of the brain ECM by alcohol may be relevant to the development of alcoholism. Although investigation of the function of brain ECM in alcohol abuse is still in early stages, a greater understanding of the interplay between ECM and alcohol might lead to novel therapeutic strategies for treating AUD.Extracellular matrix (ECM) compartments in the brain. Ethanol alters the function of all three compartments. (A). Basement membrane located on the basolateral side of endothelial cells of blood vessels is part of the blood–brain barrier (B). Interstitial matrix is found between neuronal and glial cells of the brain parenchyma. Regulation of ECM is controlled by proteases such as the matrix metalloproteinases (MMPs) and affects synaptic plasticity. (C). Perineuronal nets form lattice-like structures around neurons and also regulate neuronal activity.