Demonstrating that HDAC inhibitors inactivate Arf1 through destabilizing EGFR proteins in a histone acetylation-independent manner is very timely, which not only provides the importance of the EGFR-Arf1 complex in the development and progression of HNSCC, but also opens a promising therapeutic avenue for design of HDAC-targeted regimens to better treat HNSCC. The gene discussed is HDAC9; the disease is head and neck squamous cell carcinoma.