Data highlight that pharmacologically inhibiting the activity of class I HDACs (including HDAC2 and HDAC3) with Tac and complementary effects of silencing HDAC2 or HDAC3 alleviates mitochondrial dysfunction and the impairment in ER‐mitochondria cross‐talk in AD hippocampal neural cells. The gene discussed is HDAC2; the disease is Alzheimer disease.