Epithelial cells such as keratinocytes in the skin and lungs produce TSLP, then release it in response to a perceived threat. TSLP interacts with the TSLP receptor (TSLPR) via electrostatic interactions, forming a complex that subsequently binds to IL-7Rα. This binding process cannot proceed without a charge-charge interaction between positively charged patches of TSLP and TSLPR. This trimeric complex then induces IL-4 and IL-13 release via STAT5 and STAT6 phosphorylation in CD4 + T cells. In turn, these type 2 cytokines stimulate antibody production by B cells as well as the expansion of basophils and eosinophils in the epithelium; the result is type 2 inflammation. Further effects are the IL-13-mediated stimulation of goblet cells in bronchial epithelia, resulting in elevated expression of mucin 5 AC (MUC5AC) and thereby leading to mucosal plugs. The increasing prevalence of atopic diseases, along with TSLP's position at the top of the inflammatory cascade, render it an attractive drug target. Initial attempts at blocking the TSLP-TSLPR interaction by injection of soluble TSLPR showed a promising reduction of type 2 cytokines and reduced the infiltration of eosinophils and lymphocytes into the bronchiolar lavage fluid in mice. A more advanced approach, based on developing TSLPR-IL7Rα fusion proteins as cytokine traps, was shown to potently reduce the TSLP-mediated maturation of dendritic cells. The subsequent development of targeted antibodies led to the recent regulatory approval of the TSLP antibody Tezepelumab for the treatment of AA. However, alternate drugs are still desirable due to the general drawbacks of antibody therapies: high cost, tolerance buildup, and the likelihood of allergic reaction. This high demand for alternate therapies recently led to the discovery of the small molecule TSLPR-inhibitor BP79 and Baicalein as a TSLP inhibitor. 11, 23 BP79, alongside with structurally related TSLPR inhibitors, was found to significantly reduce the TSLP-mediated TH2 response of CD4 + T cells, and it reduced immune cell infiltration in multi-organ models. Baicalein inhibited STAT5 phosphorylation in mast-cell lines after TSLP stimulation and reduced eosinophil infiltration in ovalbumin-challenged mouse models. These results show the importance of better understanding the TSLP-TSLPR interaction to find new treatment options.