Together, phloretin inhibited AKT and ERK1/2 and activated GSK3β, and subsequently decreased the transcriptional activity of Sp1 by downregulating the expression of Sp1 gene, inducing the degradation of Sp1 and decreasing Sp1-binding to the promoters of its target genes in PCa cells. The gene discussed is MAPK3; the disease is posterior cortical atrophy.