Using mice with partial knockout of the transferrin receptor 1 (TfR1) gene Tfrc, astrocyte‐specific Tfrc knockdown, and conditional astrocytic Cpt1a partial knockout (to induce fatty acid metabolism disorders), it is revealed that increased TfR1 palmitoylation and clathrin‐mediated endocytosis drive astrocytic iron overload. The gene discussed is TFRC; the disease is inherited fatty acid metabolism disorder.