Zdhhc23, zinc finger DHHC-type palmitoyltransferase 23, is a crucial palmitoyl-transferase. Protein palmitoylation, catalyzed by it, is a significant post-translational modification involved in various biological processes, such as regulating protein-protein interactions, membrane targeting, and protein stability. It participates in multiple pathways, like those related to lipid metabolism, immune regulation, and pain signaling [1,2,3].

In hepatocellular carcinoma, Zdhhc23 mediates the palmitoylation of PHF2, enhancing its ubiquitin-dependent degradation, which then remodels lipid metabolism through the SREBP1c axis [1]. In large yellow croaker, silencing LczDHHC23 led to heightened pro-inflammatory cytokine expression, indicating its anti-inflammatory role as it promotes macrophage M2 polarization and macrophage necroptosis [2]. In a neuropathic cancer pain model, upregulation of Zdhhc23 in spinal astrocytes led to increased palmitoylation of GFAP and secretion of inflammatory factors, contributing to pain development [3]. In gastric cancer, ZDHHC23 mediated T-bet palmitoylation and promoted its degradation, affecting Th1 cell polarization and anti-tumor immunity [4].

In conclusion, Zdhhc23 is essential in processes like lipid metabolism, immune regulation, pain signaling, and anti-tumor immunity through its palmitoyltransferase function. Studies, including those using gene-related models (implied by the functional studies), have revealed its significance in these disease-related biological processes, offering potential therapeutic targets for cancers, immune-related disorders, and pain management.