In addition to PAT- mediated protein palmitoylation, we demonstrate here that ZDHHC17 also plays an apparently unique role in the PAT protein family by interacting with MAP2K4 via the N-terminal signaling and protein-protein interaction ankyrin domain, to activate JNK/p38 and regulate GBM malignant development and progression. Here, ZDHHC17 is linked to glioblastoma.