Neuron-specific enolase (NSE), also known as enolase 2 (ENO2), is a 78 kDa gamma-enolase homodimer and one of three mammalian isozymes catalyzing the interconversion of 2-phosphoglycerate and phosphoenolpyruvate. The C-terminus promotes cell survival by regulating neuronal growth factor receptor-dependent signaling pathways.   NSE localizes in the cytosol and is expressed in mature neurons and throughout the neuroendocrine system, predominantly in cells of the amine precursor uptake and decarboxylation lineage. Literature reports showed low expression of NSE in other cell types, where it may be located on the membrane and have non-glycolytic functions. These include erythrocyte, platelet, prostate, uterine, breast, striated muscle, and smooth muscle cells. However, this antibody specifically labels neuronendocrine cells in normal tissues.   NSE is the most sensitive immunohistochemical marker for middle to late stage small cell lung cancer (SCLC) and can also identify Merkel cells and melanocytes. NSE overexpression is primarily found in tumors of neurogenic and neuroendocrine origin. Incidences of normally NSE-negative cells producing NSE have been found in malignant transformations; thus, NSE should be paired with the more specific bombesin, which does not stain non-neuroendocrine cells, and/or chromogranin, which intensely stains lung carcinoid tumors.   Serum NSE is also useful in identifying small-cell lung carcinoma (SCLC), carcinoids, islet cell tumors and neuroblastomas, and are potential indicators of neural injury, such as reactive gliosis, astrocytic death, and blood-brain barrier dysfunction.