Is the CncC/Keap1 complex a major factor in conferring pesticide resistance in arthropods? - A critical review

The CncC/Keap1 signalling pathway regulates antioxidant and detoxification gene expression in arthropods and is frequently associated with metabolic insecticide resistance. This review critically assesses evidence for its role in resistance phenotypes across key pest species. Although overactivation of CncC/Keap1 correlates with increased detoxification enzyme expression and pesticide tolerance, causal mutations in the coding or regulatory regions of CncC, Keap1, or Maf remain unidentified. We evaluate the evidence supporting the role of CncC/Keap1 in pesticide resistance in insects and mites and report the latest advancements in our understanding of this system in arthropods. We further highlight the need for unbiased genetic mapping and reverse genetic approaches to resolve the mechanisms of constitutive CncC activation in resistant populations. Understanding these mechanisms is crucial for elucidating the origins of metabolic resistance and developing sustainable pest management strategies.