Zdhhc8, zinc finger DHHC-domain containing protein 8, is a protein palmitoyl transferase (PAT) [1,2,3,4,6]. Palmitoylation, a post-translational modification it catalyzes, is crucial for regulating protein stability, targeting, and trafficking [1,2,4,6]. It is involved in multiple biological pathways, with its function being essential for normal cell growth, survival, and signaling [1,2,3,4,5,6]. Genetic models, such as Drosophila ortholog knockdown and mouse models, have been valuable in studying Zdhhc8 function [3,4].

In glioblastoma, AMPKα1-mediated Zdhhc8 phosphorylation promotes SLC7A11 palmitoylation, enhancing ferroptosis resistance [1]. Knocking down Zdhhc8 in glioblastoma cells promotes intracellular ferroptosis, impairing cell survival [1].

In epilepsy models, increased Zdhhc8 expression was observed in human temporal lobe epilepsy patients and chronic epileptic mice [3]. In vitro, Zdhhc8 knockdown delayed seizure precipitation and decreased chronic spontaneous recurrent seizures, while overexpression had the opposite effect, suggesting its role in seizure generation and propagation [3].

In mesothelioma mouse models, Zdhhc8 knockdown enhanced radiosensitivity and suppressed tumor growth when combined with X-irradiation, likely through inducing chromosomal instability and apoptosis via the impaired G(2)/M checkpoint [5].

In Drosophila, knockdown of the Zdhhc8 ortholog caused tissue overgrowth and mutants were larval lethal, suggesting its role in controlling growth and viability [4].

In conclusion, Zdhhc8 plays diverse and important biological functions mainly through its role in protein palmitoylation. Model-based research, especially in mouse models, has revealed its significance in diseases like glioblastoma, epilepsy, and mesothelioma. These findings may provide new therapeutic strategies for these diseases by targeting Zdhhc8-related pathways.