IL15RA (interleukin-15 receptor subunit alpha) is a cytokine receptor subunit that mediates IL-15 signaling in diverse immune and metabolic contexts. Although IL15RA does not directly bind IL-15 with high affinity alone 1, it functions as the critical alpha chain component of the IL-15 receptor complex, conferring high-affinity IL-15 binding and enabling trans-presentation of IL-15 to tissue-resident memory T cells and NK cells 2. IL15RA exhibits widespread cellular distribution across multiple tissue types 1, with expression in chondrocytes, B cells, and immune cells 32. Mechanistically, IL15RA activates JAK-STAT signaling and MAPK cascades to regulate cell proliferation, differentiation, and survival 4. In autoimmune contexts, IL15RA+ B cells secrete CCL3 to recruit and activate CCR5+ CD4+ tissue-resident memory cells, promoting cholangiocyte pyroptosis in primary biliary cholangitis 2. In osteoarthritis, IL-15/IL15RA signaling increases matrix metalloproteinase production in cartilage and associates with pain symptoms, though not radiographic severity 3. Clinically, IL15RA genetic variants associate with symptomatic osteoarthritis and neuropathic pain risk 3, while IL15RA polymorphisms influence muscle strength and metabolism 5. IL15RA expression correlates with immune infiltration and prognosis in triple-negative breast cancer 4, and serves as a prognostic biomarker in clear cell renal carcinoma, where it promotes metastasis via NF-κΒ/ZEB1 signaling 6. Blockade of IL-15/IL15RA signaling demonstrates therapeutic potential in autoimmune liver disease 2.