Intermediate filaments (IFs) are the most intrinsically stable of the three cytoskeletal filament types. Approximately 10 nm in diameter, Ifs are generally insoluble except in strong denaturants.

Based on their absence in the yeast Saccharomyces ceravisae, Ifs appear to be unique to the metazoans (whether there are Ifs in plants remains unclear).

IFs are assembled in a heirarchical manner. Monomers associated to form parallel -helical coiled coil dimers.

Dimers associate in an anti-parallel and staggered manner to form tetramers, and tetramers go on to assemble into the final filament.

In cross-section, a typical IF contains 8 tetrameric protofibrils (or 32 subunit proteins). The C-terminal head and domains extend away from the filament axis and appear to be involved in interactions with other cytoskeletal systems.

Because of their high -helical content, immunological identification of IF proteins can be problematic (their are many helical proteins that can cross-react immunologically).

Unambiguous identification of IF proteins required DNA sequence data.

To date, bono fide IF proteins have been identified only in metazoans.

All metazoans appear to express lamins. The lamins have a central helical domain of ~352 amino acids and are localized primarily to the inner surface of the nuclear envelope.

Of the metazoans examined, only Drosophila melanogaster does not appear to have cytoplasmic IFs .

The cytoplasmic IFs of invertebrates have a long 352 amino acid central helical domain, like the lamins.

While most invertebrates appear to have relatively limited number of IF genes (the exception being C. elegans, which has lots), the IF protein family has exploded dramatically in the vertebrates.

There are four major classes of cytoplasmic IF proteins in vertebrates: the keratins (types I and II), vimentin and the vimentin-like proteins (type III) and the neuronal IF proteins (type IV). The lamins are sometimes referred to as type V IF proteins. Not shown on the diagram are the lens IF proteins since their relationship with the other classes remains ill-defined.