Abstract BACKGROUND The severe overlapping generations and rapid development of insecticide resistance in Panonychus citri pose significant challenges to chemical control. Due to that the cuticle serves as a critical defensive barrier for mite survival, elucidating its assembly mechanism may provide new targets for overcoming resistance. RESULTS This study focused on the cuticular protein PcCPR12 , which is highly expressed in the cuticle‐enriched exoskeleton fraction. Functional analysis demonstrated that silencing PcCPR12 resulted in disordered cuticular wrinkling and high mortality, with the survival rate dropping to 45.68%. In vitro experiments confirmed that the CPR12 protein possesses chitin‐binding ability, establishing its role in structural support. Transcriptome sequencing further revealed that PcCPR12 knockdown significantly down‐regulated the chitin and lipid metabolism pathways. Subsequent validation indicated that silencing the key genes PcCHT1 (chitinase) and PcFABP (fatty acid binding protein) also led to lethal phenotypes, proving their essential roles in cuticle integrity. Based on this mechanism, a fusion double‐stranded RNA (dsRNA) targeting PcCPR12–CHT1–FABP was constructed. Bioassays showed that this multi‐target strategy resulted in a lower cumulative survival rate (37.23%) and significantly impaired female fecundity compared to single‐gene interference. CONCLUSION In summary, this study demonstrates the crucial function of PcCPR12 in upholding the structural integrity and stability of the P. citri cuticle. By delivering a multi‐target strike against ‘protein–chitin–lipid’ components, the fusion RNA interference (RNAi) strategy developed here offers a theoretical foundation for P. citri management. © 2026 Society of Chemical Industry.
Wang et al. (2026) studied this question.