ZDHHC14 is a palmitoyltransferase that catalyzes palmitoylation of protein substrates, with diverse roles across multiple biological contexts. As a palmitoyl acyltransferase, ZDHHC14 localizes to the endoplasmic reticulum and Golgi apparatus and mediates protein-cysteine S-palmitoylation 1. In the nervous system, ZDHHC14 controls palmitoylation and axon initial segment clustering of the scaffolding protein PSD93 and associated Kv1 potassium channels, thereby regulating neuronal excitability 1. ZDHHC14 also palmitoylates HSV-2 glycoprotein B at cysteine 8, promoting viral membrane localization and infection efficiency 2. Regarding disease relevance, ZDHHC14 functions as a tumor suppressor in testicular germ cell tumors and prostate cancer, with frequent genomic deletions and decreased expression observed clinically 3. Conversely, ZDHHC14 is overexpressed in scirrhous gastric cancer, promoting cancer cell migration and invasion through integrin and MMP-17 regulation 4. ZDHHC14 is also implicated in preeclampsia pathogenesis, where hypomethylation-driven downregulation suppresses trophoblast proliferation and invasion 5, and in depression susceptibility through mediation of double-negative T cell populations 6. Additionally, rare ZDHHC14 copy number variations have been identified as candidate loci in macrocephaly cases 7. Recent evidence links ZDHHC14 to nanoplastic-induced emphysema through SLC31A1 palmitoylation and macrophage cuproptosis 8.