Zdhhc2, a member of the DHHC protein family, is a palmitoyl acyltransferase that mediates protein palmitoylation, a post-translational modification. This process is crucial for various biological functions, such as protein trafficking, membrane localization, and signal transduction. Zdhhc2-mediated palmitoylation is involved in multiple pathways, including the PI3K-AKT-mTOR signaling pathway [1].

In clear cell renal cell carcinoma, upregulation of Zdhhc2 confers sunitinib resistance by catalyzing AGK palmitoylation to activate the AKT-mTOR pathway [1].

In psoriasis, Zdhhc2 deficiency in mice by CRISPR/Cas9 inhibits ear skin pathology following imiquimod treatment, with reduced IFN-α production and plasmacytoid dendritic cell accumulation [2].

In macrophages, ZDHHC2 deficiency impairs immunity against Mycobacterium tuberculosis and reduces pro-inflammatory cytokine production, as it affects the autophagic degradation of B-RAF and C-RAF through palmitoylation [3].

B1-8hi cells transduced with Zdhhc2-shRNA are compromised in differentiating into germinal center B cells, suggesting Zdhhc2 is a positive regulator of this process [4].

In conclusion, Zdhhc2 is essential for multiple biological processes. Model-based research, especially gene knockout or knockdown models, has revealed its roles in diseases like renal cell carcinoma, psoriasis, tuberculosis, and in germinal center B cell differentiation. These findings provide potential therapeutic targets for treating related diseases.