Zdhhc7, also known as zinc finger DHHC-type palmitoyl transferase 7, is a palmitoyltransferase that plays a crucial role in protein S-palmitoylation. This post-translational modification is involved in various biological pathways, such as inflammasome activation, autophagy, androgen receptor regulation, and T-helper cell differentiation [1-4]. It is important for normal physiological functions and is associated with multiple disease conditions including chronic inflammatory diseases, prostate cancer, and inflammatory bowel disease. Mouse models with Zdhhc7 knockout (KO) or conditional knockout (CKO) have been instrumental in understanding its function in vivo [1-6].

In macrophages, Zdhhc7 knockout reduces NLRP3-mediated inflammasome activation as it is responsible for palmitoylating NLRP3 Cys126, which is essential for NLRP3 activation [1]. In ATG16L1-KO HeLa cells, re-expressing wild-type ATG16L1 but not the S-palmitoylation-deficient mutant rescues the defect in LC3 lipidation and autophagosome formation, indicating that Zdhhc7-mediated S-palmitoylation of ATG16L1 is crucial for autophagy [2]. In prostate cancer cells, Zdhhc7 depletion increases oncogenic properties, while restoring Zdhhc7 suppresses cell proliferation and invasion in vitro and tumor growth in vivo, as it inhibits androgen receptor gene transcription [3]. In a mouse model of inflammatory bowel disease, knockout of Zdhhc7 relieves symptoms, suggesting its role in promoting TH17 cell differentiation through STAT3 palmitoylation [4].

In conclusion, Zdhhc7 is essential for multiple biological processes through its role in protein S-palmitoylation. KO/CKO mouse models have been key in revealing its functions in diseases such as chronic inflammatory diseases, cancer, and inflammatory bowel disease. Understanding Zdhhc7 provides potential therapeutic strategies for these related disease conditions.