There remains almost no information about how individual claudins assemble into higher order structures to create 10-nm membrane particles, polymerize into the strands observed in freeze-fracture EM, or adhere across the cell–cell interspace. Currently, two papers suggest claudins, like connexins in the gap junction, form hexamers. This is based on a study of human claudin-4 expressed in insect cells (Mitic et al. 2003) and on purified native MP20, the distant claudin relative found in the lens (Jarvis and Louis 1995). There is consistent evidence that claudins can form homotypic adhesive plaques, and two studies provide evidence that this homotypic cell–cell adhesion can occur through residues in the center of the second extracellular loop (Daugherty et al. 2007; Piontek et al. 2007). Molecular modeling of claudin-5 complemented by mutagenesis suggests that adhesion requires an interaction of complementing hydrophobic residues along a helix in the center of the second loop A model of the barrier in Figure 2B is based on evidence that claudins are cell-to-cell adhesion molecules and form small pores through the barrier, but there is currently insufficient evidence to speculate on how they oligomerize to form the particles seen in freeze fracture EM images.