TWEAK and APRIL are both members of the tumor necrosis factor family, which are involved in respectively angiogenesis and immune regulation. While TWEAK is processed at the cell surface, APRIL is processed inside the cell by a furin-convertase and is solely able to perform its function as a soluble factor. Recently, TWE-PRIL has been identified, which is an endogenous hybrid transcript between TWEAK and APRIL. TWE-PRIL is a transmembrane protein that consists of a TWEAK intracellular, transmembrane and stalk region combined with APRIL as its receptor-binding domain. As such TWE-PRIL is expressed at the cell surface. Although TWE-PRIL, like APRIL, can stimulate T and B cell lines, distinct biological functions that may result from its membrane anchoring cannot be excluded. Understanding the function of this newly identified protein will contribute to the elucidation of the complexity of the tumor necrosis factor family.