Paqr5, short for Progestin and adipoQ receptor 5, is a member of the membrane-bound progesterone receptor family. It is involved in mediating the non-genomic effects of progesterone. PAQR5 has been implicated in various biological processes and disease conditions, with its expression being tissue-specific and associated with multiple signaling pathways [1-10].

In kidney cancer, PAQR5 expression is low in kidney renal clear cell carcinoma (KIRC), correlating with clinical characteristics like cancer stage, tumor grade, and nodal metastasis. Low expression is associated with poorer survival, and it may be an independent factor for a good prognosis in KIRC. It is also negatively correlated with the JAK/STAT3 signaling pathway proteins, and downregulation is related to STAT3 target upregulation, tumorigenesis, and poor differentiation. Additionally, its expression is related to tumor immune cell infiltration and immunomodulatory molecules [1,2]. In a rat UUO model of renal fibrosis, decreased PAQR5 expression was observed in the obstructed kidney, associated with a lack of nephroprotective effect of progesterone [3].

In hepatocellular carcinoma, PAQR5 expression is upregulated in tumor tissues, correlating with poor clinical outcomes. It activates the NF-κB signaling pathway, driving cell proliferation, invasion, epithelial-mesenchymal transition (EMT), and the formation of an immunosuppressive microenvironment [4].

In conclusion, PAQR5 plays a crucial role in multiple disease contexts, especially in kidney and liver cancers as well as renal fibrosis. Its involvement in various signaling pathways and its impact on cell proliferation, metastasis, and the immune microenvironment highlight its potential as a prognostic biomarker and therapeutic target. The studies using different models have provided valuable insights into the functions of PAQR5 in these disease conditions.