Occludin is an integral membrane protein closely associated with the tight junctions of epithelial and endothelial cells. Occludin is a tetraspan integral membrane protein in epithelial and endothelial tight junction (TJ) structures that can contain two extracellular loops. The protein exists in a variety of phosphorylated forms. Phosphorylation is involved in regulating both the localization and the function of occludin. Expression of occludin is up-regulated by poly-unsaturated fatty acids, increasing transendothelial cell resistance and reducing cellular permeability to large molecules. The level of occludin varies greatly depending on tissue; in brain tissue, occludin is highly expressed at cell-cell contact sites. Non-neural tissues show lower expression and discontinuous distribution. Up-regulation of epithelial occludin may play a role in enhancing paracellular permeability and be related to the damage to the tight junction.