Ligands and receptors of the TNF superfamily are therapeutically relevant targets in a wide range of human diseases and thus, understanding signaling diversity and endogenous regulatory mechanisms is of highly importance. Despite each receptor triggers a main, well-described signaling pathway, there are a plethora of other signals that these receptors can trigger depending on the cellular context, which participates in vivo to normal and pathological functions. Nevertheless, most of the molecular components and mechanisms involved in signal transduction diversity remains so far elusive. We are currently focused on understanding signal transduction diversity in order to identify new therapeutically relevant tools to stimulate or block specific cellular functions. We use different techniques, including manipulation of ligand architecture, design of peptide mimetics, studies of ligand -dependent and -independent receptor oligomerization and identification of supramolecular membrane complexes. Our work aims at identifying novel endogenous mechanisms that controls signalling diversity with the final goal of generating new tools to intervene under pathologic conditions.