Zdhhc6, a zinc finger-aspartate-histidine-cysteine 6 protein, functions as a palmitoyltransferase. It plays a crucial role in palmitoylation, a post-translational lipid modification that impacts protein stability, localization, and function. Zdhhc6 is involved in multiple biological pathways, such as lipid metabolism-related pathways, and has significance in various biological processes and disease conditions. Genetic models, like knockout (KO) mouse models, are valuable tools for studying Zdhhc6's functions [1,3,4,5,6,7,8].

In colon cancer, Zdhhc6 promotes tumorigenesis by palmitoylating and stabilizing PPARγ at the Cys-313 site in its DNA binding domain. This leads to increased expression of ATP citrate lyase (ACLY) and enhanced fatty acid biosynthesis. Inhibition of Zdhhc6 expression in in vivo trials significantly reduces the cancer-causing effects [1].

In hepatocellular carcinoma, deletion of Zdhhc6 suppresses AEG-1 palmitoylation, exacerbating the progression of DEN-induced HCC in mice. This indicates that Zdhhc6-mediated AEG-1 palmitoylation negatively regulates its protein stability and affects its interaction with SND1, altering RISC activity and tumor suppressor expression [3].

In sepsis, ZDHHC6 knockdown decreases MYD88 palmitoylation and TLR/MYD88 activation upon lipopolysaccharide stimulus, suggesting that ZDHHC6-mediated MYD88 palmitoylation is a therapeutic target [2].

In conclusion, Zdhhc6, as a palmitoyltransferase, is essential in regulating protein palmitoylation, which impacts multiple biological processes. Its role in diseases such as colon cancer, hepatocellular carcinoma, and sepsis has been revealed through KO mouse models. Understanding Zdhhc6's functions provides potential therapeutic targets for these diseases.