Neurofilaments (NF) are the main cytoskeletal constituents in neuronal cells. Their primary function is to maintain the diameter of axons and dendrites and transmit electrical impulses along axons. CNS Neurofilaments are heteropolymers composed of 4 subunits: NF-light (~68kDa), NF-medium (~150kDa), NF-heavy (~200kDa), and alpha-internexin. The NF-heavy and NF-medium C-terminal domains have multiple tandem 6-8 amino acid sequence repeats containing conserved KSXXP motifs. The serine residue is the major axonal phosphorylation site. Dendritic and perikaryal NF-heavy is not phosphorylated on these sites, therefore a release of phosphorylated NF-heavy can be used as a biomarker of axonal damage and degeneration. pNF-heavy is a cytoskeletal protein present in abundant amounts and consequently detectable once released into the blood, is highly immunogenic, and protease resistant. These characteristics make pNF-heavy a desirable CNS biomarker. Recent studies have shown that when compared with healthy controls, mild Traumatic Brain Injury (mTBI) patients have elevated serum levels of pNF-heavy on Days 1 and 3 after TBI. Elevated serum levels of pNF-heavy have been seen in human subjects with acute ischaemic stroke, acute brain injury after cardiac arrest, and Amyotrophic Lateral Sclerosis. Elevated CSF levels have also been demonstrated in animal models of spinal cord injury and brain injury.