ZDHHC16, zinc finger DHHC-type palmitoyltransferase 16, is involved in protein palmitoylation, a post-translational lipid modification. It participates in multiple biological pathways, influencing processes like cell proliferation, differentiation, and DNA damage response, which are crucial for normal biological functions and disease prevention [1,2,5,6].

In cancer, ZDHHC16 promotes PCSK9 palmitoylation at cysteine 600, increasing its binding to PTEN, leading to PTEN degradation, AKT activation, and ultimately sorafenib resistance in liver cancer [1]. In bone-related research, ZDHHC16 knockdown in human bone marrow mesenchymal stem cells promotes osteogenic differentiation by enhancing CREB phosphorylation, and in dental pulp stem cells, its inhibition promotes osteogenic differentiation and reduces ferroptosis [2,4]. In the nervous system, ZDHHC16 up-regulation in a cerebral apoplexy model promotes neurocyte ferroptosis and inflammation by suppressing CREB [3].

In conclusion, ZDHHC16 plays diverse and significant roles in multiple biological processes and disease conditions. Its functions in promoting sorafenib resistance in liver cancer, inhibiting osteogenic differentiation, and promoting neurocyte ferroptosis in cerebral apoplexy highlight its importance as a potential therapeutic target in these disease areas. Research on ZDHHC16 using gene-knockout models has been instrumental in uncovering these functions, contributing to a better understanding of disease mechanisms and potential treatment strategies.