Summary

• Intermediate filaments (IFs) are assembled from fibrous proteins that exhibit a central -helical rod domain with a conserved substructure. This rod domain facilitates the formation of dimeric coiled-coil complexes.
• In metazoan cells, IF proteins constitute two distinct filament systems: one in the nucleus and one in the cytoplasm. In both cases, the major function of these filaments is thought to be the buffering of mechanical stress.
• In conjunction with associated proteins, IFs generate networks that serve to generate and support the shape of cells.
• Recent nanomechanical experiments have demonstrated that IFs are characterized by a high propensity to withstand both tensile and bending stress.
• In line with this, disease mutations in human IF proteins indicate that the nanomechanical properties of cell-type-specific IFs are central to the pathogenesis of these diseases.
• Apart from structural functions, the analysis of complex diseases, such as cardiomyopathies, has revealed that IFs also have a significant role in cell-type-specific physiological functions and even contribute to the regulation of gene-expression programmes.