TRAIL/Apo2L, also known as Tumor Necrosis Factor Super-Family 10 (TNFSF10), is a pleiotropic cytokine thatbelongs to the TNF superfamily. The full length TRAIL expressed in vivo is a Type II transmembrane protein, although the soluble form also exists and functions. TRAIL has four major receptors: two death receptors DR4 and DR5, two decoy receptors DcR1 and DcR2. TRAIL binds to the death receptors, recruits the FAS-associated death domain, activates caspases 8 and 10, and eventually leads to apoptosis. Because of its antitumor potential, TRAIL is actively studied as a therapeutic agent. On the other hand, abnormal expression of TRAIL in small arteries can induce the proliferation of smooth muscle cells, resulting in increasing vascular remodeling and pulmonary arterial hypertension.