FASL was initially cloned and purified from a cytotoxic T cell hybridoma, PC60-d10S. FASL is a type II transmembrane glycoprotein of approximately 40 kD and belongs to the TNF family of membrane-associated cytokines. A soluble fragment of FASL (sFASL, 26-29 kD) has been described using in vitro proteolytic assays, and MMP7 was proposed to participate in this process. Nevertheless, TIMPs (tissue inhibitors of metalloproteinases) did not alter FASL shedding. FASL is proteolytically cleaved by ADAM10, and it is the major protease responsible for FASL cleavage in murine fibroblasts and human T cells. The cleavage site is between Ser126 and Leu127. This site is outside of the self assembly (SA) domain that allows sFASL to form trimers. It has been suggested that FASL performs its biological activity as a homotrimer. Shedding of FASL modulates FASL/FAS dependent apoptosis and affects activation-induced cell death (AICD) in a superantigen stimulation model. It has published that sFASL has proapoptotic and antiapoptotic properties, depending of cell type and cell microenvironment. sFASL can be detected in the serum of patients with dysregulated inflammatory diseases. Mutations in human FAS and FASL are associated to autoimmune lymphoproliferative syndrome (ALPS). In these patients, the homeostasis of T and B lymphocytes is disturbed, leading to hepatosplenomegaly and lymphadenopathy.? Dysregulation of FAS/FASL has been connected to multiple diseases such as osteoarthritis, pulmonary fibrosis, diabetic polyneuropathy, acute coronary syndrome, bladder and gastric cancer among others.