Zdhhc7, encoding zinc finger DHHC-type palmitoyltransferase 7, is a key enzyme in protein S-palmitoylation. Protein S-palmitoylation is a post-translational modification that affects protein localization, activity, and stability, thus playing a crucial role in multiple cellular processes and disease-related pathways [1,2,4,5,6]. It is involved in regulating inflammation, autophagy, cell cycle, and androgen response, which are vital for normal physiological function and disease prevention [1,2,3]. Mouse models with Zdhhc7 knockout (KO) are valuable tools to study its functions.

In the context of NLRP3 inflammasome activation, Zdhhc7 knockout in macrophages reduced NLRP3 activation, highlighting its role in promoting inflammasome activation through NLRP3 Cys126 palmitoylation [1]. In autophagy, ATG16L1-KO HeLa cells with re-expression of wild-type ATG16L1 but not the S-palmitoylation-deficient mutant rescued LC3 lipidation and autophagosome formation, indicating Zdhhc7-mediated ATG16L1 S-palmitoylation is essential for autophagy [2]. In prostate cancer, depletion of Zdhhc7 increased oncogenic properties of prostate cancer cells, while restoring it suppressed cell proliferation and invasion in vitro and in vivo [3]. In a mouse model of inflammatory bowel disease, knockout of Zdhhc7 relieved symptoms, revealing its role in promoting TH17 cell differentiation through STAT3 palmitoylation [4]. In pyroptosis, perturbation of GSDMD palmitoylation by Zdhhc7 affected the process, influencing the survival of mice with septic shock and their sensitivity to bacterial infection [5]. In Alzheimer's disease, hippocampal silencing of Zdhhc7 in 3×Tg-AD mice prevented cognitive deficits [6].

In conclusion, Zdhhc7 is essential for multiple biological processes through protein S-palmitoylation. Zdhhc7 KO mouse models have significantly contributed to understanding its roles in various disease areas such as chronic inflammatory diseases, autophagy-related disorders, prostate cancer, inflammatory bowel disease, septic shock, and Alzheimer's disease. These findings suggest that targeting Zdhhc7 could be a potential therapeutic strategy for these diseases.