Palmitoyltransferase ZDHHC12 (ZDHHC12)

ZDHHC12 is a protein-cysteine S-palmitoyltransferase that catalyzes the transfer of palmitate to cysteine residues on substrate proteins, a post-translational modification known as S-palmitoylation. It regulates mitochondrial oxidative metabolism and ROS homeostasis, especially in cancer cells, where its elevated expression is linked to poor outcomes and chemoresistance. In ovarian cancer, ZDHHC12 inhibition enhances cisplatin sensitivity by increasing ROS and mitochondrial dysfunction. Beyond oncology, ZDHHC12 participates in synaptic organization by palmitoylating gephyrin, required for postsynaptic density and GABA receptor clustering. The enzyme acts via a zinc finger DHHC domain, belonging to a broader family of protein acyltransferases that control diverse cellular processes through dynamic protein lipidation. Its molecular and disease associations position ZDHHC12 as both a mechanistic and therapeutic target in cancer biology and neurobiology.

Other names

ZNF400DHHC-12PSEC0008FLJ14524DHHC domain-containing cysteine-rich protein 12Zinc finger DHHC domain-containing protein 12Zinc finger protein 400

Inhibition (by siRNA, chemical inhibitor, or FASN inhibition): Disrupts mitochondrial function, increases ROS, and enhances cancer cell sensitivity to cisplatin. Palmitoylation of substrate proteins: ZDHHC12 transfer palmitate to protein cysteine residues, affecting protein stability, trafficking, and interaction (e.g., HDAC8 palmitoylation promotes stability in HCC; gephyrin palmitoylation alters synaptic clustering).