IL21R encodes the interleukin-21 receptor, a critical component of cytokine signaling that regulates immune cell development and function. The receptor mediates IL-21-induced activation of the STAT signaling pathway, particularly STAT3 phosphorylation, promoting T cell proliferation, memory differentiation, and reducing apoptosis 1. IL21R signaling plays diverse roles in immune responses, including enhancement of cytotoxic CD8+ T cell function against viral infections like hepatitis B 2. However, in certain disease contexts, IL21R can have detrimental effects by promoting immunosuppressive IgA+ B cell development through a STAT1-c-Jun/c-Fos regulatory axis, contributing to hepatocellular carcinoma progression 3. The receptor is expressed on various immune cell populations and shows compartmentalized expression patterns, with HIV-1 reservoir cells in lymph nodes upregulating IL21R as part of a survival signature 4. Genetic variations in IL21R are associated with bone mineral density regulation 5, and aberrant methylation patterns in IL21R serve as potential biomarkers for breast cancer diagnosis 6. The receptor shares structural similarities with other γc family cytokine receptors, forming degenerate contacts consistent with its role in immune system regulation 7.