AbstractPlectin is a cytoskeletal protein of > 500 kDa that forms dumbbell-shaped homodimers comprising a central parallel α-helical coiled coil rod domain flanked by globular domains, thus providing a molecular backbone ideally suited to mediate the protein's interactions with an array of other cytoskeletal elements. Plectin self-associates and interacts with actin and intermediate filament cytoskeleton networks at opposite ends, and it binds at both ends to the hemidesmosomal transmembrane protein integrin beta-4, and likely to other junctional proteins. The central coiled coil rod domain can form bridges over long stretches and serves as a flexible linker between the structurally diverse N-terminal domain and the highly conserved C-terminal domain. Plectin is also a target of p34cdc2kinase that regulates its dissociation from intermediate filaments during mitosis.