GUCA2B (guanylate cyclase activator 2B) encodes uroguanylin, an endogenous peptide hormone that activates the intestinal guanylate cyclase-C (GUCY2C) receptor to regulate fluid and electrolyte transport 1. This hormone functions as both an endocrine and paracrine regulator of intestinal salt-water balance and is expressed by specialized BEST4+ absorptive cells in the human intestinal epithelium 2. GUCA2B expression is significantly reduced in colorectal cancer tissues, where it functions as a tumor suppressor through the GUCY2C signaling axis 34. MicroRNAs hsa-miR-27a-3p and hsa-miR-182-5p promote CRC progression by downregulating GUCA2B expression 5. Beyond cancer, GUCA2B levels are decreased in inflammatory bowel disease and obesity-associated non-alcoholic fatty liver disease (NAFLD), where uroguanylin supplementation mitigates hepatic steatosis, mitochondrial dysfunction, and fibrosis 61. Post-bariatric surgery increases GUCA2B levels in parallel with metabolic improvements. Additionally, specific GUCA2B haplotypes are associated with essential hypertension susceptibility 7, and elevated uroguanylin after sleeve gastrectomy correlates with reduced dietary fat preference, suggesting roles in satiety and food preference regulation 8.