Zdhhc12, a zinc finger DHHC-type palmitoyltransferase, is involved in protein S-palmitoylation, a post-translational modification where palmitate is attached to cysteine residues of proteins. This process is crucial for the regulation of protein function, localization, and stability, and is associated with multiple biological pathways, including those related to inflammation, cancer progression, and immune responses [1-5].

In mice, Zdhhc12 deficiency enhances inflammatory symptoms and lethality following alum-induced peritonitis and LPS-induced endotoxic shock, as ZDHHC12 is identified as the S-acyltransferase for NLRP3 palmitoylation, promoting its degradation through chaperone-mediated autophagy. This reveals ZDHHC12 as a repressor of NLRP3 inflammasome activation [2,4]. In ovarian cancer, knockdown of ZDHHC12 inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis, indicating its role in cancer progression [1]. Also, inhibition of ZDHHC12 in ovarian cancer cells disrupts mitochondrial function and ROS homeostasis, sensitizing cells to cisplatin [3]. In glioma cells, knockdown of ZDHHC12 reduces their growth, migration, and invasion capabilities [5].

In conclusion, Zdhhc12 is essential for regulating protein palmitoylation, which has far-reaching effects on inflammation and cancer-related processes. The use of Zdhhc12 knockout mouse models has provided valuable insights into its role in inflammatory diseases and cancer, highlighting its potential as a therapeutic target in these disease areas.