Palmitoylation of MDH2, catalyzed by zDHHC18 at C138, results in the activation of mitochondrial respiration and promotes the malignancy of ovarian cancer. Additionally, it acts as a negative regulator of the cGAS-STING pathway by mediating the palmitoylation and inactivation of CGAS. zDHHC18 may also exhibit palmitoyltransferase activity towards the beta-2 adrenergic receptor/ADRB2, thereby regulating G protein-coupled receptor signaling. Here, MDH2 is linked to ovarian cancer.