MAPK8 and Alzheimer disease: Furthermore, in vitro experiments showed that in PC12 cells and cortical neurons downregulated by RFWD2, the expression levels of p-JNK, SGK1, and p-Tau increased, and those of LC3B/Beclin-1 decreased; ROS levels increased, and apoptosis was induced; inhibiting JNK or SGK1 expression reversed these changes.<h4>Conclusion</h4>RFWD2 regulates SGK1 expression through the JNK pathway, thereby regulating mitochondrial autophagy and apoptosis, altering the expression levels of p-Tau and Aβ proteins, inducing AD-like symptoms in mice, and promoting AD development.