GUCY1A2 encodes the alpha-2 subunit of soluble guanylate cyclase, which plays a critical role in the nitric oxide (NO)-cGMP signaling pathway 12. The protein functions as part of the guanylate cyclase complex that converts GTP to cyclic GMP in response to NO stimulation 2. In chr11 rhinosinusitis with nasal polyps, GUCY1A2 is upregulated and associated with increased recurrence risk, suggesting dysfunction in NO-mediated signaling contributes to disease pathology 2. A gain-of-function variant (E486D) in GUCY1A2 causes increased NO affinity and elevated cGMP levels, leading to autonomous ovarian hyperfunction and precocious puberty resembling McCune-Albright syndrome 3. The gene has been implicated in various disease contexts including rheumatoid arthritis 4, gastric cancer metabolism 5, and gestational diabetes 6. In pulmonary arterial hypertension, GUCY1A2 is regulated by BMPR2 and serves as the main target of the FDA-approved drug riociguat 1. Additionally, a circular RNA derived from GUCY1A2 (circGUCY1A2) acts as a tumor suppressor in non-small cell lung cancer by sponging miR-200c-3p and promoting PTEN expression 7.