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.