When comparing signalling activity over the four different IL1RL1 protein structures, we observed that a maximal response to the IL33 isoforms occurred in cells expressing IL1RL1 with both asthma risk alleles for the extracellular‐variant rs1041973 (C) and the asthma‐associated TIR signalling domain haplotype tagged by rs10192157 (C). Here, IL33 is linked to asthma.