Intestinal tight junctions control the passage of large molecules such as intact proteins, particles and cells through the paracellular space. This passive transport is known as intestinal paracellular permeability, and while it accounts for only 10 percent of total protein uptake it serves as the major portal for intact protein and antigen delivery into the body. Protein entry is in close proximity to the submucosal lymphocytes, which comprise 80 percent of immunoglobulin producing cells in the human body.

Increased intestinal paracellular permeability leads to antigen presentation for processing and antibody response. Tight junctions in other organs have a similar function: the regulation of paracellular transport. In the capillary endothelia of the blood brain barrier, tight junctions are the anatomical barrier interfacing blood and CNS.

Tight junction dysfunction has been implicated in a host of disease states, including a variety of autoimmune diseases. Ischemia - reperfusion injury also appears to be associated with tight junction dysfunction, while many cytokines, bacterial toxins, infections, and drugs have also been implicated in tight junction injury or destruction.