IL1RAP and irritable bowel syndrome: In this study, we demonstrated that: (1) SPS Model Effectiveness: SPS model mimics IBS symptoms under stress, similar to clinical cases; (2) BGA Mechanisms in IBS: Phosphoproteome and bioinformatic methods analysis for the first time reveals p-S179-ZO1 and p-S566-IL-1RAP could be the potential pathologic “checkpoints” in mediated BGA in IBS-like stressed mice; and (3) ZO-1 and IL-1RAP Phosphorylation's Impact: SPS stress alters ZO-1 phosphorylation, disrupting the intestinal barrier, increasing IL-1β release, and promoting phosphorylated IL-1RAP complexes, leading to IBS.