["Archives of Insect Biochemistry and Physiology, Volume 122, Issue 1, May 2026. ", "Exposure to chlorantraniliprole inhibits key detoxification enzymes and downregulates most related genes in L. dispar asiatica larvae, reducing detoxification capacity and enhancing insecticide toxicity.\n\n\n\n\n\nABSTRACT\nThe Asian spongy moth, Lymantria dispar asiatica, is a polyphagous defoliator capable of damaging a wide range of tree species and is recognized as a major forest pest worldwide. Chlorantraniliprole, a widely used anthranilic diamide insecticide, is highly effective against lepidopteran pests; however, the molecular detoxification mechanisms employed by L. dispar asiatica in response to this compound remain poorly understood. In this study we investigated the integrated transcriptomic and enzymatic detoxification response of third‐instar L. dispar asiatica larvae following exposure to response to acute LC₅₀ exposure concentrations of chlorantraniliprole. Toxicity was first determined using a leaf‐dip bioassay. Transcriptomic analysis identified 167769 differentially expressed genes (DEGs), which were significantly enriched in metabolic and detoxification‐related pathways, including drug metabolism, glutathione metabolism, and cytochrome P450 pathways. Quantitative real‐time PCR (q‐RT‐PCR) further validated the upregulation of several key detoxification genes, including CYP6AN15v1, CYP6AE51, GSTe1, and UGT2. Interestingly, transcriptome‐wide analysis also revealed a broad downregulation of numerous genes within the cytochrome P450 and UDP‐glycosyltransferase (UGT) families. Consistent with these transcriptional patterns, enzyme activity assays demonstrated significant inhibition of cytochrome P450, glutathione S‐transferase (GST), and UDP‐glycosyltransferase (UGT) enzyme activities, whereas carboxylesterase (CarE) activity was markedly induced. Collectively, these findings demonstrated that chlorantraniliprole elicits a multifaceted detoxification response in L. dispar asiatica characterized by selective transcriptional activation of specific detoxification genes alongside the broad suppression of major detoxification enzymes. The inhibition of CYP450, GST and, UGT activities, appears to represent a key mechanistic basis underlying the high efficacy of chlorantraniliprole against this pest."]