SMPD1 and cancer: This is the first finding that TSWU-BR4-triggered ceramide-enrich lipid raft membrane platform formation to initiate formation of p85α–unphosphorylated PTEN complexes by inducing lipid raft membrane targeting of ASM, leading to the dislocalization of GRP78 from the lipid raft and ER membranes to the cytosol and suppression of the interactions between p85α and GRP78, thereby attenuating the GRP78-regulated oxidative stress balance and cholesterol metabolism and the GRP78−p85α−Akt−GTP-Rac1−NF-κB−MMP-2-mediated cancer cell invasion.