PIGR (polymeric immunoglobulin receptor) functions primarily as a transmembrane receptor that facilitates the transcytosis of polymeric immunoglobulins, particularly IgM and IgA, from the basolateral to apical surface of epithelial cells 1. The receptor enables transport of antibodies to mucosal surfaces where they provide immune protection against pathogens. PIGR is highly expressed in specific cholangiocyte populations (DUOX2+ACE2+ small cholangiocytes) in the liver, where its dysregulation appears clinically significant 2. The protein serves as a biomarker in multiple disease contexts: elevated plasma PIGR levels are associated with non-alcoholic fatty liver disease and cirrhosis, showing 170% and 298% increases respectively 3. In primary biliary cholangitis, anti-PIGR autoantibodies are significantly elevated regardless of AMA-M2 status, suggesting an autoimmune target role 2. PIGR mutations occur under positive selection in inflammatory bowel disease-affected colon and are associated with peritoneal metastasis risk in gastric cancer 45. The gene also shows epigenetic dysregulation in IBD-associated colorectal cancer 6 and serves as a diagnostic biomarker for distinguishing papillary renal cell carcinoma from other kidney tumor subtypes 7. Additionally, PIGR appears in cholangiocarcinoma biomarker panels for early diagnosis 8.