Histamine is an inflammatory mediator that is ubiquitously expressed and has a broad range of pharmacologic effects. Specifically, it plays a role in the central nervous, gastrointestinal, respiratory and immune systems. Histamine release is mediated by the stimulation of mast cells and basophils. Histamine-releasing factor (HRF) is a cytokine-like molecule that causes the release of histamine, IL-4 and IL-13 from basophils as well as the secretion of IL-8 and a calcium response in eosinophils. HRF belongs to the translationally controlled tumor protein (TCTP) family and is detected as a protein of 21 kDa in mice and 23 kDa in human. It is expressed in several healthy and tumoral cells, including erythrocytes, hepatocytes, macrophages, platelets, keratinocytes, erythroleukemia cells, gliomas, melanomas, hepatoblastomas and lymphomas, and it is localized in the cytoplasm. HRF plays a pivotal role in allergic diseases, and due to its wide distribution in brain, is thought to be involved in neurodegenerative disorders, such as Alzheimer's disease and Down Syndrome.