Internexin, alpha-internexin, is a Class IV intermediate filament approximately 66 KDa. The protein was originally purified from rat optic nerve and spinal cord. The protein copurifies with other neurofilament subunits, as it was originally discovered, however in some mature neurons it can be the only neurofilament expressed. The protein is present in developing neuroblasts and in the central nervous system of adults. The protein is a major component of the intermediate filament network in small interneurons and cerebellar granule cells, where it is present in the parallel fibers. Structure Alpha-internexin has a homologous central rod domain of approximately 310 amino acid residues that form a highly conserved alpha helical region. The central rod domain is responsible for coiled-coil structure and is flanked by an amino terminal head region and a carboxy terminal tail. This rod domain is also involved in the 10 nm filament assembly structure. The head and tail regions contain segments that are highly homologous to the NF-M’s structure. The head region is highly basic and contains many serine and threonine polymers while the tail region has distinct sequence motifs like a glutamate rich region. The alpha domain is composed of heptad repeats of hydrophobic residues that aid the formation of a coiled coil structure. The structure of Alpha-internexin is highly conserved between rats, mice and humans. Alpha-internexin can form homopolymers, unlike the heteropolymer the neurofilaments form. This formation suggests that α-internexin and the three neurofilaments form separate filament systems. Not only can alpha-internexin form homopolymers but it form a network of extended filaments in the absence of other intermediate filament proteins and efficiently co-assemble with any type IV or type III subunit, in vitro. In Ching et al., a model of the intermediate filaments assembly is proposed. This model includes the following steps: Step 1: in the first step of IF assembly two parallel, unstaggered intermediate filament polypeptides chains form a dimer via their a-helical rod domains; these dimers can be either homodimers or heterodimers. Step 2: the dimers may associate laterally to form antiparallel, unstaggered tetramers or antiparallel, staggered tetramers. Step 3: the dimers may also associate longitudinally with a short head-to-tail overlap of the a-helical rod domains. Step 4: these lateral and longitudinal associations lead to the formation of protofibrils (octamers) and ultimately 10 nm intermediate filaments. The close connection between the neurofilament triplet proteins and α-internexin is quite obvious. α-internexin is functionally interdependent with