Linear ubiquitination is a post-translational protein modification recently 
discovered to be crucial for innate and adaptive immune signaling. The function 
of linear ubiquitin chains is regulated at multiple levels: generation, 
recognition, and removal. These chains are generated by the linear ubiquitin 
chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming 
the linear ubiquitin linkage de novo. LUBAC is not only relevant for activation 
of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in 
various signaling pathways, but importantly, it also regulates cell death 
downstream of immune receptors capable of inducing this response. Recognition of 
the linear ubiquitin linkage is specifically mediated by certain ubiquitin 
receptors, which is crucial for translation into the intended signaling outputs. 
LUBAC deficiency results in attenuated gene activation and increased cell death, 
causing pathologic conditions in both, mice, and humans. Removal of ubiquitin 
chains is mediated by deubiquitinases (DUBs). Two of them, OTULIN and CYLD, are 
constitutively associated with LUBAC. Here, we review the current knowledge on 
linear ubiquitination in immune signaling pathways and the biochemical 
mechanisms as to how linear polyubiquitin exerts its functions distinctly from 
those of other ubiquitin linkage types.