Although it is only relatively recently that intermediate filaments (IFs) have been recognized as as uperfamily of lO-nm fibers ubiquitous in multicellular eukaryotes, their existence has been known for nearly a century, since the time when cytoskeletal fibrillar structures---or neurofilaments-were revealed upon silver staining of neurons. The first X-ray diffraction patterns of IFs were obtained from wool fibers, revealing that keratins, which were sub sequently found to be members of this family, are richly a-helical poly peptides that intertwine in a coiled-coil fashion to form the subunit structure of lO-nm filaments (1-3). When electronmicroscopy was more extensively used on vertebrate cells, the widespread occurrence of IFs began to be recognized.

IFs derive their name from their diameter (10 nm). Originally used to emphasize their intermediate nature between thin actin filaments and thick myosin filaments (4), the name later focused on width differences between actin filaments (6 nm), IFs, and microtubules (23 nm). Together, these three filamentous networks constitute the basic features of the higher eukaryotic cytoskeleton. In contrast to actins and tubulins, which are highly evolutionarily conserved, IF proteins, which include the nuclear lamins, sometimes share as little as 20% sequence identity. Members of the IF superfamily exhibit cell-type-specific and often complex patterns of expres sion. In various combinations in vitro, they have the intrinsic ability to self-assemble into lO-nm filaments containing several 1O, 000s of individual IF polypeptide chains. Their filament-forming capacity thus seems to be critical for some common function; their diversity in sequence and expression suggests that in addition, IFs perform specialized cellular functions. In this review, we summarize studies that probe the structure and dynamics of IFs. Discoveries in recent years have projected new and exciting insights into the functions of IFs and their involvement in human disease.