GUCY2C is a transmembrane guanylate cyclase that catalyzes cGMP synthesis from GTP in intestinal epithelial cells 12. The receptor is activated by endogenous peptides guanylin and uroguanylin, as well as by bacterial enterotoxins 34. Beyond its canonical role in intestinal fluid and electrolyte homeostasis, GUCY2C has emerged as a critical therapeutic target across multiple disease contexts. In visceral pain syndromes, GUCY2C expressed in intestinal neuropod cells regulates neuronal excitability; FDA-approved GUCY2C agonists like linaclotide ameliorate pain in chr12 constipation patients through neuropod-specific signaling mechanisms 5. Functionally, GUCY2C acts as a tumor suppressor, with loss of GUCY2C signaling implicated in colorectal tumorigenesis initiation 6. Clinically, GUCY2C serves as an ideal immunotherapy target because it is expressed nearly universally in colorectal cancers while restricted to intestinal epithelium in normal tissues 7. Multiple GUCY2C-targeted immunotherapies are in development, including bispecific CD3-engaging antibodies 89 and CAR-T cells 1011, with early clinical trials demonstrating objective response rates in heavily pretreated metastatic colorectal cancer patients 12.