IL1RL1 (interleukin 1 receptor like 1) encodes ST2, a critical receptor in the IL-33/ST2 signaling pathway that regulates type 2 immune responses and inflammation. The gene produces both membrane-bound (ST2L) and soluble (sST2) isoforms 1. ST2L functions as the primary receptor for IL-33, mediating signaling in various immune cells including mast cells, group 2 innate lymphoid cells, regulatory T cells, and eosinophils 2. The soluble sST2 isoform acts as a decoy receptor, binding IL-33 and inhibiting IL-33/ST2L signaling to limit type 2 inflammation 1. IL-4 specifically upregulates IL1RL1 expression in eosinophils via STAT6 signaling, promoting a proallergic phenotype 3. In cancer, IL1RL1+ regulatory T cells coordinate with cancer-associated fibroblasts through amphiregulin/EGFR signaling to promote immune tolerance 4. Mast cells control lung type 2 inflammation by producing sST2 in response to PGE2 5. IL1RL1 polymorphisms are associated with reduced allergic rhinitis risk in Chinese populations 6 and correlate with obesity and inflammation markers 7. The IL33 and IL1RL1 genes represent highly replicated asthma susceptibility loci, highlighting their clinical significance in allergic diseases 2.