or tissue invasion; an oxidative stress protein in endothelial cells; a lens crystalline; a heat shock protein; and a binding partner of cytoskeletal and chromatin structures to aid in transcription. Clinical significance Cancer ENO1 overexpression has been associated with multiple tumors, including glioma, neuroendocrine tumors, neuroblastoma, pancreatic cancer, prostate cancer, cholangiocarcinoma, thyroid carcinoma, lung cancer, hepatocellular carcinoma, and breast cancer. In many of these tumors, ENO1 promoted cell proliferation by regulating the PI3K/AKT signaling pathway and induced tumorigenesis by activating plasminogen. Moreover, ENO1 is expressed on the tumor cell surface during pathological conditions such as inflammation, autoimmunity, and malignancy. Its role as a plasminogen receptor leads to extracellular matrix degradation and cancer invasion. Due to its surface expression, targeting surface ENO1 enables selective targeting of tumor cells while leaving the ENO1 inside normal cells functional. Moreover, in tumors such as non-Hodgkin lymphomas (NHLs) and breast cancer, inhibition of ENO1 expression decreased tolerance to hypoxia while increasing sensitivity to radiation therapy, thus indicating that ENO1 may have aided chemoresistance. Considering these factors, ENO1 holds great potential to serve as an effective therapeutic target for treating many types of tumors in patients. ENO1 is located on the 1p36 tumor suppressor locus near MIR34A which is homozygously deleted in Glioblastoma, Hepatocellular carcinoma and Cholangiocarcinoma. The co-deletion of ENO1 is a passenger event with the resultant tumor cells being entirely dependent on ENO2 for the execution of glycolysis. Tumor cells with such deletions are exceptionally sensitive towards ablation of ENO2. Inhibition of ENO2 in ENO1-homozygously deleted cancer cells constitutes an example of synthetic lethality treatment for cancer. Autoimmune disease ENO1 has been detected in serum drawn from children diagnosed with juvenile idiopathic arthritis. Alpha-enolase has been identified as an autoantigen in Hashimoto's encephalopathy. Single studies have also identified it as an autoantigen associated with severe asthma and a putative target antigen of anti-endothelial cell antibody in Behçet's disease. Reduced expression of the enzyme has been found in the corneal epithelium of people suffering from keratoconus. Gastrointestinal disease CagA protein was found to activate ENO1 expression through activating the Src and MEK/ERK pathways as a mechanism for H. pylori-mediated gastric diseases. Hemolytic anemia Enolase deficiency is a rare inborn error of metabolism disease, leads to hemolytic anemia in affected homozygous carriers of loss of function mutations in ENO1. As with other glycolysis enzyme deficiency diseases, the condition is aggravated by redox-cycling agents such as nitrofurantoin.