HACE1 plays a significant role in regulating NRF2, a key TF involved in antioxidant responses. Research indicates that HACE1 promotes NRF2 accumulation by supporting its protein synthesis independently of its E3 ligase activity. Additionally, decreased HACE1 expression in HD brains leads to Nrf2 degradation and inhibits Nrf2 activity, impacting redox balance and antioxidant response mechanisms. HACE1 is essential for astrocyte mitochondrial function and promotes the stability of NRF2, highlighting its importance in maintaining cellular redox homeostasis. The gene discussed is HACE1; the disease is Huntington disease.