Figure 4. Genotype-structurotype-phenotype correlation emphasizes the role structural mechanisms play in the pathogenesis of human diseases.

Mutations in IFs can disrupt IF structure through a variety of mechanisms that ultimately inhibit or distort IF assembly (top). Common outcomes from IF mutations are the formation of cytoplasmic (or nuclear) aggregates, misfolded filaments, re-organized IF networks, and decreased mechanical support to the cell (often leading to cell fragility).