Zdhhc2, a member of the DHHC protein family, functions as a palmitoyl acyltransferase. It mediates palmitoylation, a post - translational modification that plays crucial roles in various biological processes. This modification is involved in regulating protein - protein interactions, subcellular localization, and the function of numerous proteins, thereby impacting multiple cellular pathways [1,2,3,4,5,6,7,8]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying Zdhhc2's function.

In renal cell carcinoma, ZDHHC2 - mediated AGK palmitoylation activates the AKT - mTOR signaling pathway, reducing sunitinib sensitivity [1]. In psoriasis, Zdhhc2 deficiency in mice inhibits the disease's pathology, with reduced plasmacytoid dendritic cell (pDC) accumulation and IFN - α production [2]. In macrophages infected with Mycobacterium tuberculosis, ZDHHC2 deficiency impairs immunity and cytokine production, as it mediates the palmitoylation of B - RAF and C - RAF affecting their autophagic degradation [5]. In germinal center B cell differentiation, Zdhhc2 - shRNA - transduced B1 - 8hi cells show compromised differentiation [7].

In conclusion, Zdhhc2 plays essential roles in multiple biological processes and disease conditions. Studies using KO/CKO mouse models have revealed its significance in cancer drug resistance, inflammatory disorders, and immune - related responses, providing insights into potential therapeutic targets for diseases like renal cell carcinoma, psoriasis, and tuberculosis.