IL2RB encodes the beta subunit of the interleukin-2 receptor, a critical component of the IL-2 signaling complex 1. IL2RB functions as a coreceptor that binds IL-2 in association with IL-2Rα and the common gamma chain (γc), with IL-2Rα stabilizing a secondary binding site that presents IL-2 to IL2RB for signal transduction 1. The receptor mediates mitogenic signaling and receptor-mediated endocytosis, and likely cooperates with IL15RA to stimulate neutrophil phagocytosis via IL-15 signaling. IL2RB plays essential roles in CD8+ T cell expansion and cytotoxic function; PGE2 in the tumor microenvironment impairs IL-2 sensing by downregulating IL2RB-γc dimer assembly, reducing T cell proliferation and anti-tumor immunity 2. Genetically, IL2RB mutations cause Immunodeficiency 63 with lymphoproliferation and autoimmunity, with intrauterine-onset cases representing the most severe presentations 3. IL2RB is also implicated in Philadelphia chr22-like acute lymphoblastic leukemia as one of multiple kinase/cytokine receptor genes whose alterations activate oncogenic signaling 4. Additionally, IL2RB variants associate with regulatory T cell defects and ALPS-like autoimmune lymphoproliferative phenotypes 5. Common IL2RB polymorphisms influence lung cancer susceptibility in population studies 6.