This study identified ZDHHC5 as a key PAT in LUAD for its over-expression and malignant prognosis in LUAD patients, overturning its previously refuted prognostic value. As digging the stemness substrate of ZDHHC5, we found INCENP was correlated with the gene expression of ZDHHC5 in LUAD. Importantly, the analysis of the S-palmitoylation site brings us to speculation that ZDHHC5 catalyzes the S-palmitoylation at Cys15 of INCENP. By analyzing the nuclear localization signals and observing immunofluorescence results, we found that ZDHHC5 locates in the nucleoplasm, in addition to the plasma membrane. Our work highlights the essential role of ZDHHC5 in LUAD and reveals that ZDHHC5 modulates the S-palmitoylation of INCENP. However, further research including in vivo and in vitro experiments is needed to validate ZDHHC5 as a molecular target in the therapy of LUAD patients.
