FDX1 (ferredoxin 1) is a small mitochondrial iron-sulfur cluster protein that serves as an essential electron transfer mediator in steroidogenesis and plays a critical role in the newly identified copper-dependent cell death pathway called cuproptosis 1. In steroid hormone synthesis, FDX1 transfers electrons from adrenodoxin reductase to CYP11A1, facilitating cholesterol side-chain cleavage for steroid production. In cuproptosis, FDX1 acts as a key regulator by reducing Cu2+ to Cu+ ions, which promotes toxic oligomerization of lipoylated proteins in the tricarboxylic acid cycle, particularly dihydrolipoyl transacetylase (DLAT), while simultaneously reducing iron-sulfur cluster protein levels 1. FDX1's role in cuproptosis has significant clinical implications across multiple cancer types. In hepatocellular carcinoma, FDX1 downregulation promotes tumor progression through ROS-mediated activation of mitophagy and PI3K/AKT signaling, making it a potential prognostic biomarker 2. In triple-negative breast cancer, AKT1-mediated FDX1 phosphorylation confers cuproptosis resistance, suggesting combination therapy with AKT1 inhibitors and copper ionophores as a therapeutic strategy 3. Additionally, FDX1 upregulation in residual tumors after radiotherapy increases cuproptosis sensitivity, presenting opportunities for overcoming radiation resistance 4. These findings position FDX1 as both a metabolic regulator and a promising therapeutic target in cancer treatment strategies involving copper-based therapies.