Pigr, the polymeric immunoglobulin receptor, is a transmembrane transporter responsible for transporting polymeric IgA through the intestinal epithelium. It plays a crucial role in mucosal immunity, as it helps maintain the first line of antigen-specific immune defense at mucosal surfaces [1,5]. It also serves as the precursor of secretory component, which enhances the immune functions of secretory IgA [5].

In pIgR-deficient mice, ethanol feeding led to increased liver injury, steatosis, and inflammation compared to wild-type littermates. This indicates that pIgR-mediated secretion of IgA in the liver limits bacterial translocation, thus preventing ethanol-induced liver disease [3]. In hepatocellular carcinoma (HCC), pIgR-enriched extracellular vesicles promoted cancer stemness and tumorigenesis in recipient cells, and this effect was hindered by an anti-pIgR antibody. The role of EV-pIgR depends on the activation of the PDK1/Akt/GSK3β/β-catenin signaling axis [2]. Also, in HCC, PIGR overexpression was associated with poor disease-free survival, and ribosome signaling was identified as a common pathway in PIGR overexpression and knockdown samples in Bel-7404 cells [4].

In conclusion, Pigr is essential for mucosal immunity by facilitating IgA transport. Its deficiency in mouse models has revealed its significance in preventing ethanol-induced liver disease. In cancer, especially HCC, Pigr or its associated extracellular vesicles seem to play a role in promoting tumor-related phenotypes, highlighting its potential as a therapeutic target in these disease areas.