Fujita et al. (2013) identified that the ubiquitin ligase, membrane-associated RING-CH (MARCH) 8, ubiquitinates TfRC and promotes its lysosomal degradation (Tachiyama et al., 2011). However, whether WDR45 mutation impairs autophagic degradation of TfRC and TfRC involves in iron accumulation in patients with BPAN are still unknown. In this study, we confirmed that TfRC was indeed degraded via autophagy, WDR45 mutation resulted in TfRC accumulation, and ferritin H (FTH) chain reduction, therefore, led to Fe2+ overload which further promoted ferroptosis in HeLa cells. This evidence concerns the gene TFRC and neurodegeneration with brain iron accumulation 5.