P21-activated kinase 2 (PAK2) targets Nrf2/Keap1 ubiquitination by mediating 3-hydroxy-3-methylglutaryl reductase degradation 1 (HRD1) expression, thereby alleviating detrimental ER stress and HF, offering another potential therapeutic strategy for HF [97]. The gene discussed is SYVN1; the disease is hydrops fetalis.