F2RL3 (Proteinase-Activated Receptor 4, PAR4) is a member of the Proteinase-Activated Receptor subfamily and is activated by trypsin and thrombin. Binding by thrombin leads to the activation of platelets, leukocytes, endothelial cells and mesenchymal cells at sites of vascular injury. These cellular responses are triggered through proteolytic activation of the receptors by thrombin. It is believed that F2RL3 functions as a cofactor for the cleavage and activation of F2RL3. In clear cell renal cell carcinoma, high expression of F2RL3 is associated with poor prognosis and aggressive characteristics. In immunohistochemistry, F2RL3 has membranous positivity in Herring bodies of the posterior pituitary, Bergmann glia of the cerebellum and variable staining in neurons of the CA2 hippocampus, lateral hypothalamic nucleus and basal nucleus of Meynert in the brain. In peripheral tissues, it has moderate to strong positivity in hepatocytes, the bronchial respiratory epithelium, pancreatic exocrine cells, neuroendocrine cells of the small intestine, the placenta, the urinary bladder, sweat glands, the thymus, and also on neutrophils in some tissues including the anterior pituitary and spleen. References: J Cancer. 2018; 9(18): 3400–3406, PMID: 30271502