{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLCO2A1 encodes the prostaglandin transporter protein—often referred to as PGT or OATP2A1—that is essential for mediating the cellular uptake of prostaglandins such as PGE₂, PGH₂, and even PGE₃. By transporting these lipid mediators from the extracellular milieu into cells, SLCO2A1 facilitates their subsequent metabolic inactivation by 15‐hydroxyprostaglandin dehydrogenase. This uptake process is critical for controlling local prostaglandin levels and thereby regulating diverse signaling pathways involved in inflammation, cell proliferation, apoptosis, and other physiological processes. In several in vitro and in vivo studies, researchers have demonstrated that decreased expression or inactivation of SLCO2A1 leads to diminished prostaglandin uptake, which in turn causes elevated extracellular prostaglandin levels and dysregulation of downstream signaling cascades—for example, alterations in cyclic AMP levels and changes in phosphorylation of kinases. These findings underscore the key molecular function of SLCO2A1 in maintaining prostaglandin homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, mutations or polymorphisms in SLCO2A1 are now recognized as the molecular basis for a spectrum of disorders associated with aberrant prostaglandin catabolism. Loss‐of-function mutations impair prostaglandin uptake and clearance, thereby resulting in pathologically high prostaglandin concentrations. This defect has been implicated in primary hypertrophic osteoarthropathy, pachydermoperiostosis, and chronic nonspecific ulcerative enteropathy (now often designated as chronic enteropathy associated with SLCO2A1 or CEAS). In addition, altered SLCO2A1 function has been linked to changes in prostaglandin signaling in various cancers—including colorectal, lung, and gastric malignancies—as well as differences in drug responses, such as in patients with glaucoma or thiazide‐induced hyponatremia. Such studies, spanning diverse tissues from decidualized endometrium to neuronal and vascular endothelia, highlight how defective or dysregulated SLCO2A1 activity can influence not only local inflammatory and proliferative responses but also contribute to systemic phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "25"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vijaykumar R Holla, Michael G Backlund, Peying Yang, et al. 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