NGLY1 deficiency is a rare genetic disorder caused by mutations in the NGLY1 gene. This disorder presents a wide range of clinical symptoms, and its severity varies among affected individuals. Previous studies have focused on understanding the influence of NGLY1 on energy metabolism, revealing dysregulation in lipid metabolism following NGLY1 deletion. In this study, we investigated the consequences of the loss of NGLY1 on ferroptosis and iron homeostasis using human hepatocellular carcinoma cells, HepG2.