Irritable Bowel Syndrome (IBS) is a highly prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits, increasingly recognized as a systemic condition involving neuroimmune and endocrine dysregulation. Recent Genome-Wide Association Studies (GWAS) have identified shared genetic susceptibility between IBS and mood disorders, implicating genes involved in neural signaling, stress responses, and immune regulation. Among these, FAM120A has emerged as a potential molecular bridge linking oxidative stress, Src family kinase signaling, and immune homeostasis. This review synthesizes current evidence on the roles of FAM120A, FKBP5, Src kinases, and C-terminal Src Kinase (CSK) in gut–brain interaction, immune signaling, and blood pressure regulation. We propose a unifying hypothesis in which chronic activation of the FAM120A–FKBP5 axis contributes to immune exhaustion, dysregulated T-cell receptor signaling, and inflammation-driven hypertension.

Keywords: Irritable bowel syndrome; Gut–brain axis; Protein phosphorylation; FAM120A (OSSA); FKBP5; Src family kinases