Tetranychus urticae, the two-spotted spider mite, poses a significant threat to crops due to its remarkable capacity to metabolize xenobiotics. This adaptive ability enables spider mites not only to thrive on numerous plant species but also to rapidly develop resistance to acaricides employed for their control. The extent and speed of the rapid transcriptional reprogramming of detox-gene expression as a response to exposure and adaptation to various toxins, raises fundamental questions about gene regulation mechanisms in polyphagous herbivores. In a recent study, we identified a nuclear receptor of the HR96 family lacking a DNA binding domain as a master-regulator of detoxification gene expression, as well as other genes associated with host plant use. Because many arthropods have only a single HR96 receptor, we hypothesize that the large expansion of HR96 genes in the T. urticae genome plays a key role in the species’ rapid adaptation to multiple plant hosts and pesticides. In this project I want to study and functionally validate the importance the HR96 receptor family using reverse genetic tools combined with gene expression analysis. With cutting-edge technologies I will study in vivo localization of expression and identify the necessary interactors of the DNA binding domain-lacking HR96 regulators to initiate expression. Together, this work will assess the role of HR96 expansions in xenosensing, gene expression regulation and thus adaptation of an important crop pest.