IL13RA2 encodes a cell surface receptor that plays dual roles in interleukin-13 mediated signaling. The protein primarily functions as a decoy receptor, binding IL-13 with high affinity but lacking intracellular signaling domains, thereby inhibiting canonical IL-13 and IL-4 mediated JAK-STAT pathway activation 1. This decoy function is critical in regulating immune responses and inflammation, as demonstrated by its downregulation in keloid fibroblasts leading to enhanced STAT6 phosphorylation and fibrotic responses 1. Additionally, IL13RA2 serves as a functional signaling receptor in alternative pathways, activating p38 MAPK/ATF3 cascades that induce lipocalin-2 production in hepatic stellate cells during liver fibrosis 2. The receptor shows significant clinical relevance as a therapeutic target, particularly in cancer immunotherapy. It is highly expressed in glioblastoma and serves as an antigen for CAR-T cell therapies, with clinical trials demonstrating bioactivity and tumor regression in recurrent glioblastoma patients 34. IL13RA2 is also implicated in inflammatory diseases, with inflammatory fibroblasts expressing high levels during ulcerative colitis and being associated with anti-TNF treatment resistance 5. The receptor's expression can be therapeutically modulated, as shown with Moscatilin treatment enhancing IL13RA2 expression to suppress vascular calcification 6.