Neurofilaments usually contain three intermediate filament proteins: L, M, and H which are involved in the maintenance of neuronal caliber. NF-H has an important function in mature axons that is not subserved by the two smaller NF proteins. Neurofilament-H (NF-H), also known as neurofilament heavy polypeptide, and Neurofilament-L (NF-L), also known as neurofilament light polypeptide, members of the intermediate filament family, are major components of neuronal cytoskeletons. Neurofilaments are dynamic structures; they contain phosphorylation sites for a large number of protein kinases, including protein kinase A, protein kinase C, cyclin-dependent kinase 5, extracellular signal regulated kinase, glycogen synthase kinase-3, and stress-activated protein kinase gamma. In addition to their role in the control of axon caliber, neurofilaments may affect other cytoskeletal elements, such as microtubules and Actin filaments. Changes in neurofilament phosphorylation or metabolism are frequently observed in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease and Alzheimer's disease.