In Drosophila, the canonical Toll signaling pathway is initiated by the binding of a spatzle ligand to Toll (Tl) or a Toll-like receptor leading to the nuclear localization of the NF-κB (dl or Dif) transcription factor. Negative regulators of Toll-NF-κB Signaling lead to the increased cytosolic retention of the NF-κB proteins dl or Dif and/or repression of target gene transcription. (Adapted from FBrf0091014 and FBrf0223077).