IL2RG encodes the common gamma chain (γc), a shared receptor subunit essential for cytokine signaling in immune cells. The γc chain forms heterodimeric receptors with specific alpha chains for multiple interleukins including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 1. These receptors primarily signal through the JAK1/JAK3-STAT5 pathway, with additional non-canonical pathways involving STAT1, STAT3, PI3K/AKT, and MEK/ERK 1. IL2RG is critical for lymphocyte development and homeostasis, being required for survival of immature thymocytes, naïve T-cells, memory T-cells, pro-B-cells, and innate lymphocytes 1. Mutations in IL2RG cause X-linked severe combined immunodeficiency (X-SCID), characterized by profound defects in T-cell, B-cell, and natural killer cell function 2. The clinical significance is substantial, as IL2RG deficiency results in severe immunodeficiency requiring treatment such as hematopoietic stem cell transplantation or emerging gene therapies using lentiviral vectors 2. The γc chain can be downregulated by factors like PGE2 in tumor microenvironments, impairing IL-2 sensing and T-cell function 3. IL2RG-deficient mouse models (IL2rg-null) are widely used in research for studying human immune system development and disease 4 5.