Thirty-two genes involved in key sig naling pathways were found to be significantly deregulated (P < .05), and 6 key signaling proteins (Akt (Ser473), c-Jun (Ser63), Erk1/2 (Th202/Tyr204), Thr185/Tyr187), IκB-α (Ser32/Ser36), MEK1 (Ser217/Ser221), mTOR (Ser2448)) were downregulated at the protein level (P < .05).<h4>Conclusion</h4>The findings reveal that major signaling pathways, including MAPK, PI3K/AKT/mTOR, and JAK/STAT, are significantly sup pressed in the esophageal epithelium of achalasia patients, despite preserved epithelial barrier integrity. The gene discussed is JUN; the disease is Achalasia.