Ectopic expression of WT, but not of S‐acylation‐deficient zDHHC22, reduced the proliferation of ER‐negative BrCa cell lines, enhanced mTOR S‐acylation, decreased AKT signaling, and restored MCF‐7R cells sensitivity to oestrogen therapy. The gene discussed is ZDHHC22; the disease is invasive breast carcinoma.