Model of TNIP1 regulation. Under basal, unstimulated conditions (left panel), TNIP1 functions as a negative regulator of inflammatory signaling and is subject to constitutive autophagic degradation through interaction with autophagy receptors such as p62/SQSTM1. Upon poly(I:C)-induced activation of TLR3 (right panel), activated TBK1 phosphorylates TNIP1 in the vicinity of its LIR, increasing TNIP1 affinity for human LC3 and GABARAP proteins. This, in turn, leads to a LIR-dependent increase in TNIP1 degradation through selective autophagy. The removal of TNIP1 relieves the negative effect on inflammatory signaling, allowing the establishment of a robust inflammatory response upon antiviral signaling.