Zdhhc12, a zinc finger DHHC-type palmitoyltransferase, is involved in the S-palmitoylation of various proteins. S-palmitoylation is a post-translational modification where a palmitate group is attached to cysteine residues, which can regulate protein localization, stability, and function. This process participates in multiple biological pathways, including those related to inflammation, tumorigenesis, and immune responses [1,2,3,4,5,6,7,8].

In mice, Zdhhc12 deficiency enhances inflammatory symptoms and lethality following alum-induced peritonitis and LPS-induced endotoxic shock, suggesting its role in controlling inflammation by regulating NLRP3 inflammasome activation through promoting NLRP3 degradation via chaperone-mediated autophagy [2,4]. In ovarian cancer, knockdown of ZDHHC12 inhibits CLDN3 accurate membrane localization, protein stability, and ovarian cancer cells tumorigenesis, indicating its role in tumor progression [1]. Also, inhibition of ZDHHC12 in ovarian cancer cells can disrupt mitochondrial function and ROS homeostasis, sensitizing cells to cisplatin [3].

In conclusion, Zdhhc12 is crucial for regulating protein function through S-palmitoylation in processes related to inflammation and cancer. Studies using Zdhhc12-deficient mouse models have revealed its significance in controlling inflammation and its potential as a target in ovarian cancer treatment, providing insights into disease mechanisms and possible therapeutic strategies.