Plectin is a giant protein found in nearly all mammalian cells which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments. In addition, plectin links the cytoskeleton to junctions found in the plasma membrane that structurally connect different cells. By holding these different networks together, plectin plays an important role in maintaining the mechanical integrity and viscoelastic properties of tissues. Mutations in PLEC have been associated with epidermolysis bullosa simplex with muscular dystrophy. A missense variant of PLEC has been recently proposed as a cause of atrial fibrillation in some populations. Isolated left ventricular non-compaction accompanying epidermolysis bullosa simplex with muscular dystrophy was also noted. Plectin has been proposed as a biomarker for pancreatic cancer. Although normally a cytoplasmic protein, plectin is expressed on the cell membrane in pancreatic ductal adenocarcinoma (PDAC) and can therefore be used to target PDAC cells.