Neuron-Specific Enolase (NSE), also known as Gamma-enolase, is a 78kDa enzyme of the glycolytic pathway expressed predominantly in neurons and cells of the neuroendocrine system. The C-terminal part of the molecule has been shown to promote survival of neuronal cells by regulating neuronal growth factor receptor dependent signaling pathways, resulting also in extensive actin cytoskeleton remodeling. NSE is a tumor marker used in diagnosis and prognosis of cancer; however its mechanism in malignant progression remains elusive. Studies in Traumatic Brain Injury (TBI) have shown NSE levels increase during the first 12 hours after trauma and decrease within hours. NSE is not secreted, but when there is axonal damage to neurons NSE levels are up regulated to maintain homeostasis, therefore it can be used to directly assess damage to neurons. Mortality and unfavorable outcome were significantly associated with greater NSE concentrations. NSE is also present in Erythrocytes, and even mild hemolysis can significantly increase serum NSE levels.