PLAUR, also known as the urokinase-type plasminogen activator receptor (uPAR), is involved in multiple biological processes. It plays a role in cell adhesion, migration, and extracellular matrix degradation, and is associated with pathways such as the PI3K/AKT/mTOR signaling pathway. PLAUR is important in inflammation, cancer, and other conditions, and genetic models could potentially provide more insights into its functions [6,9].

In gastric cancer, TCF7L2 transcriptionally activates PLAUR, promoting anoikis resistance and metastasis, making them candidate targets for therapeutic strategies [1]. In chronic pruritus, PLAUR-TLR2-OSM signaling promotes skin-nerve communication, cutaneous inflammation, and itch [2]. Regarding hereditary angioedema, although no significant difference in PLAUR alternative transcript frequency was seen between patients and healthy volunteers, the splicing pattern changed during monocyte-to-macrophage differentiation [3]. In bladder urothelial carcinoma, PLAUR is elevated, associated with poor survival and immune infiltration, suggesting it could be a biomarker or immunotherapeutic target [4]. In glioblastoma, PLAUR is identified as a hub gene regulating the mesenchymal phenotype and mediating ligand-receptor interaction between tumor-associated macrophages and glioma cells [5]. In clear cell renal cell carcinoma, PLAUR upregulation is associated with poor prognosis, and its knockdown attenuates tumor cell proliferation, migration, and invasion by inhibiting the PI3K/AKT/mTOR signaling pathway [6]. In non-small-cell lung cancer, exosomal PLAUR mRNA is increased in gefitinib-resistant patients, and silencing PLAUR in resistant cells induces apoptosis via the EGFR/p-AKT/survivin signaling pathway [7]. In kidney renal clear cell carcinoma, PLAUR is upregulated, associated with poor survival, and the PVT1/SNHG15-hsa-miR-532-3p axis may regulate it, while PLAUR is also related to tumor-infiltrating immune cells [8]. In endothelial cells, an endothelial-specific enhancer regulates PLAUR expression [9]. In glioblastoma, PLAUR marks two intra-tumoral subtypes with different molecular cooperators [10].

In conclusion, PLAUR is involved in a wide range of biological functions, especially in processes related to cancer and inflammation. Studies on PLAUR, including those potentially using gene knockout or conditional knockout mouse models, contribute to understanding the mechanisms of these diseases, providing potential targets for treatment in cancer and other conditions such as chronic pruritus and hereditary angioedema.