The IL-15R is a heterotrimeric complex that includes a beta subunit (IL-2R/15Rβ/CD122) shared with the IL-2 receptor, a common gamma subunit (γc/CD132) shared with IL-2, IL-4, IL-7, IL-9 and IL-21, and a unique alpha subunit (IL-15Rα) that confers receptor specificity to IL-15. IL-15Rα is structurally similar to IL-2Rα; the ectodomain of IL-15Rα consists of a single protein-binding Sushi domain (essential for IL-15/ IL-15Rα function) a membrane-proximal proline-threonine-rich (PT) region, and a linker/hinge region that connects the sushi domain and the PT region. IL-15Rα is widely expressed in mice and humans independently of IL-2R/IL-15Rβ-γc. IL-15Ra binds IL-15 with high affinity and in this way the cytokine is retained on the surface of the cells and trans-presented to IL-2R/15Rβ-γc on nearby effector NK and T cells. IL-15Rα and IL-15 play a key role in the development and homeostasis of memory CD8 T cells, natural killer cells, invariant NKT cells, and a subset of intestinal intraepithelial lymphocytes, as described by their significant deficiency in IL-15-deficient mice. In mast cells, IL-15R/IL-15 acts as a growth factor and an inhibitor of apoptosis. In addition, the complex IL-15R/IL-15 induces B lymphocyte proliferation, differentiation, and increases immunoglobulin secretion. A soluble form of human IL-15Ra arises from proteolytic shedding of the membrane-anchored receptor. It is released from IL-15Ra-expressing human cell lines. This release is strongly induced by PMA, ionomycin, and to a lesser extent by IL-1b and TNFa. Abnormal expression of both IL-15Rα and IL-15 is associated with the pathogenesis of celiac disease. Also, high levels of soluble IL-15Rα are detected in serum of patients with T cell large granular lymphocyte leukemia.