AKT1 and gastroesophageal reflux disease: The report indicated that in cases of GERD, human esophageal microvascular endothelial cells (HEMEC) react to acidic pH stress through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, and extended exposure to acidic pH leads to pronounced phosphorylation of Akt in HEMEC.[37] Studies have shown that TNFSF12 protects cardiomyocytes from apoptosis in a manner reliant on the PI3K/AKT signaling pathway.[38] These studies provide a possible explanation for our MR analysis results: TNFSF12 protects HEMEC from apoptosis via the PI3K/AKT pathway, thereby reducing the risk of GERD.