Therefore, the current study aimed to investigate EMPA’s regulatory effect on the Sesn2/AMPK/Nrf2/heme oxygenase 1 (HO-1) signaling pathway as well as its modulatory role in ferroptosis, inflammation, ER stress, and autophagy in the context of BLM-induced PF. The gene discussed is SESN2; the disease is pemphigus foliaceus.