ZDHHC15 is an X-linked palmitoyltransferase that catalyzes S-palmitoylation of diverse protein substrates, regulating their membrane localization and function 1. In the nervous system, ZDHHC15 palmitoylates PSD-95, promoting synaptic clustering and excitatory synapse formation through enhanced dendritic trafficking 2. The enzyme also regulates dopaminergic signaling; Zdhhc15-knockout mice exhibit increased novelty-induced locomotion and elevated striatal dopamine release 3. Beyond neuronal function, ZDHHC15 mediates palmitoylation of c-MET in glioblastoma stem cells, where CK2α phosphorylation of ZDHHC15 enhances c-MET activation and tumorigenicity 4. ZDHHC15 also palmitoylates KIBRA and GP130, regulating Hippo/YAP signaling and IL-6/STAT3 pathways respectively, promoting tumor metastasis and glioma progression 56. ZDHHC15 expression correlates with poor prognosis in glioma patients 7. Clinically, loss-of-function variants in ZDHHC15 cause X-linked intellectual developmental disorder 8, and emerging evidence links ZDHHC15 haploinsufficiency to autism spectrum disorder 9. Therapeutic targeting of ZDHHC15-mediated palmitoylation represents a novel strategy against glioblastoma and palmitic acid-driven metastasis.