Polymeric immunoglobulin receptor in liver diseases: a double-edged sword with therapeutic potential at the gut–liver axis

The polymeric immunoglobulin receptor (pIgR) mediates the transepithelial transport of polymeric immunoglobulin A (IgA) and plays a central role in gut immune homeostasis. Its involvement in liver diseases has become increasingly evident with advances in our understanding of the gut-liver axis. This review synthesizes current evidence on the molecular structure and regulation of pIgR expression. It examines the functional heterogeneity of pIgR across viral hepatitis, alcohol-related liver disease, and metabolic dysfunction-associated steatotic liver disease, autoimmune liver diseases, and hepatocellular carcinoma. Current evidence suggests that pIgR can exert protective effects by preserving the intestinal barrier integrity; however, under specific pathological conditions, it may contribute to autoimmune responses and tumor progression. The present review further evaluates the potential of pIgR for clinical translation as a biomarker and therapeutic target, discusses its immunopharmacological potential, and identifies unresolved questions that may guide future investigation.