GUCY1A1 encodes the alpha-1 subunit of soluble guanylate cyclase (sGC), a key enzyme in the nitric oxide (NO)-cGMP signaling pathway 1. The protein catalyzes cGMP biosynthesis in response to NO, activating downstream protein kinase G (PKG) signaling essential for vasodilation and vascular homeostasis 2. GUCY1A1 is expressed in vascular endothelial cells, smooth muscle, and neuronal elements including retinal ganglion cells 3. Mechanistically, GUCY1A1 functions within a regulatory axis involving LDHA and GPX4, where PKG-mediated phosphorylation of LDHA leads to GPX4 phosphorylation, suppressing ferroptosis and protecting against ischemia-reperfusion injury 1. The gene is transcriptionally regulated by FoxO4, a Forkhead transcription factor that directly binds promoter motifs 2. GUCY1A1 variants (rs7692387) show age-dependent associations with acute coronary syndromes, with the AA genotype conferring reduced risk in patients over 55 years 4. Disease relevance extends to Moyamoya disease 6 with achalasia. Emerging evidence identifies GUCY1A1 as part of immune-metabolic checkpoints in colon adenocarcinoma 5 and demonstrates sGC activators like runcaciguat improve neuroretinal function in diabetic and ischemic retinopathy 3, suggesting therapeutic potential in vascular and metabolic disorders.