IL22RA1 encodes the alpha subunit of the interleukin-22 receptor, which forms functional receptor complexes with IL10RB for IL-22 signaling and with IL20RB for IL-20/IL-24 signaling, activating JAK/STAT pathways 1. The receptor plays critical roles in maintaining tissue homeostasis across multiple organs. In hepatocytes, IL22RA1 prevents steatosis by regulating oxysterol metabolism through the ATF3/CYP7B1 axis, with deficiency leading to lipid accumulation and NAFLD progression 2. In intestinal epithelium, IL22RA1 signaling in MATH1+ cells (goblet and progenitor cells) maintains mucosal barrier function by promoting mucin O-glycosylation via B3GALT5 expression and supports tissue regeneration after injury 3. In pancreatic β cells, IL22RA1 preserves insulin secretion capacity through STAT3/c-Jun-mediated regulation of cytochrome b5 reductase 3 (CYB5R3), with deficiency impairing mitochondrial function in type 2 diabetes 4. Clinically, IL22RA1 shows pathological significance in cancer, where high expression correlates with poor prognosis and enhanced stemness in pancreatic cancer via STAT3 signaling 5. Pan-cancer analysis reveals IL22RA1 upregulation across 11 cancer types, suggesting its potential as a therapeutic target 1.