Association of the receptor Fas with its ligand Fas-L triggers an apoptotic pathway that plays an important role in immune regulation, development, and progression of cancers. Fas-L (CD95L, Apo-1L) is a type II transmembrane protein of 280 amino acids (runs at approximately 40 kDa upon glycosylation) that belongs to the TNF family, which also includes TNF-α, TRAIL, and TWEAK. Binding of Fas-L to its receptor triggers the formation of a death-inducing signaling complex (DISC) involving the recruitment of the adaptor protein FADD and caspase-8. Similar to other members of the TNF family, Fas-L can be cleaved by metalloproteinases producing a 26 kDa trimeric soluble form.