The spider mite Tetranychus urticae is a serious crop pest with an exceptional ability to metabolize the toxins it encounters in the environment. This allows spider mites to thrive on a remarkable number of different plant species, but also to rapidly develop resistance to acaricides that are used for their control. Spider mites can quickly change the expression of detoxification genes upon exposure and adaptation to toxins. Recently, we found that a nuclear receptor of the HR96 family is associated with the constitutive and high expression of a battery of detoxification genes in a multi-resistant strain. This receptor was structurally divergent from known HR96 receptors, and surprisingly, we found a whole expanded family of paralogs in the genome of T. urticae. We hypothesize that this unusual receptor family allows to perceive different toxins and thus might provide functional specificity in activating defense responses. Here, we therefore study the role of these receptors by reverse genomic tools combined with transcriptome analysis, and design functional assays to study interactions of these receptors with their ligands. The manipulation of the expression levels of these receptors in genetically modified mite strains, will be investigated for its effects on the toxicity of acaricides and the fitness on different host plants.