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In previous studies, we found that the cysteinyl leukotriene receptor 1 (CysLTR1) regulates autophagy in the retinal pigment epithelial cell line ARPE\u201019 under basal cellular conditions. However, the underlying mechanism by which CysLTR1 regulates autophagy is unknown. Thus, in the present study, the effects of CysLTR1 inhibition on the endosomal\u2010lysosomal system are analyzed in detail to identify the role of CysLTR1 in cell homeostasis and autophagy regulation. CysLTR1 inhibition in ARPE\u201019 cells by Zafirlukast, a CysLTR1 antagonist, depleted the lysosomal pool. Furthermore, CysLTR1 antagonization reduced endocytic capacity and internalization of epidermal growth factor and decreased levels of the transferrin receptor, CD71. Serum starvation abolished the effect of Zafirlukast on the autophagic flux, which identifies the endocytic regulation of serum components by CysLTR1 as an important autophagy\u2010modulating mechanism. The role of CysLTR1 in inflammation and cell stress has been exceedingly studied, but its involvement in the endosomal\u2010lysosomal pathway is largely unknown. This current study provides new insights into basal activity of CysLTR1 on cellular endocytosis and the subsequent impact on downstream processes like autophagy.<\/jats:p>","DOI":"10.1111\/tra.12881","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T08:36:30Z","timestamp":1674808590000},"page":"177-189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cysteinyl leukotriene receptor 1 is a potent regulator of the endosomal\u2010lysosomal system in the <scp>ARPE<\/scp>\u201019 retinal pigment epithelial cell line"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-8411","authenticated-orcid":false,"given":"Andreas","family":"Koller","sequence":"first","affiliation":[{"name":"Research Program for Experimental Ophthalmology and Glaucoma Research, Department of Ophthalmology and Optometry University Hospital of the Paracelsus Medical University  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