Linear ubiquitin chains are implicated in the regulation of the NF-κB pathway, 
immunity, and inflammation. They are synthesized by the LUBAC complex containing 
the catalytic subunit HOIL-1-interacting protein (HOIP) and are disassembled by 
the linear ubiquitin-specific deubiquitinase OTULIN. Little is known about the 
regulation of these opposing activities. Here we demonstrate that HOIP and 
OTULIN interact and act as a bimolecular editing pair for linear ubiquitin 
signals in vivo. The HOIP PUB domain binds to the PUB interacting motif (PIM) of 
OTULIN and the chaperone VCP/p97. Structural studies revealed the basis of 
high-affinity interaction with the OTULIN PIM. The conserved Tyr56 of OTULIN 
makes critical contacts with the HOIP PUB domain, and its phosphorylation 
negatively regulates this interaction. Functionally, HOIP binding to OTULIN is 
required for the recruitment of OTULIN to the TNF receptor complex and to 
counteract HOIP-dependent activation of the NF-κB pathway.