IFs form complex three-dimensional networks with cell type specific subcellular arrangements providing barrier function in simple and stratified epithelia. (A) Keratin IFs (blue) are subapically enriched in a dense filamentous network in the simple epithelium of the intestine. They localize just below the microvillar brush border that protrudes into the nutrient-filled intestinal lumen. The cylindrical epithelial cells are connected by junctional complexes, which encompass keratin-anchoring desmosomes (green), and rest all on a basal lamina; (B) The keratin IFs (blue) of the stratified epithelium of the cornea form dense 3D-networks that traverse the entire cytoplasm and are attached to desmosomes (green) at cell-cell contact sites. Keratin fragments with antibacterial activity are released into the tear fluid. The keratin cytoskeleton of the basal cells is anchored to hemidesmosomes (red), which attach to the underlying extracellular matrix of the basement membrane; (C) The keratin IF cytoskeleton of the epidermis, which is the prototype of a multilayered cornified epithelium, increases in density in the flattened suprabasal cell layers and becomes compacted as part of the cornified envelope of the dead cells in the uppermost stratum corneum which are continuously shed from the epithelium. While desmosomes (green) are present in all cell layers, hemidesmosomes (red) are restricted to the cuboidal basal cell layer.