CISD1 is a mitochondrial iron-sulfur cluster-binding protein that functions as a transamidase catalyzing the reversible transfer of amino groups from L-cysteine to 2-oxoglutarate, with pyridoxal 5'-phosphate serving as an essential cofactor. Beyond its enzymatic role, CISD1 acts as a redox sensor regulating mitochondrial iron-sulfur cluster assembly and iron trafficking, particularly under oxidative stress. The protein can transfer [2Fe-2S] clusters to recipient proteins only in its oxidized state, linking its conformational state to cellular redox homeostasis. CISD1 has emerged as a critical node in multiple disease pathways. In neurodegenerative disease, CISD1 accumulation blocks mitophagy and impairs autophagy flux in Pink1/parkin mutant models; genetic or pharmacological inhibition by rosiglitazone and NL-1 ameliorates locomotor deficits and extends lifespan 1. Iron-sulfur cluster loss and disulfide-linked dimer formation of CISD1 mediate pathological phenotypes in Pink1 loss-of-function models 2. In chr10 obstructive pulmonary disease, smoke-induced CISD1 reduction in macrophages promotes M1 polarization and mitochondrial dysfunction through autophagy pathway activation 3. Dysregulated CISD1 also drives ferroptosis in multiple contexts: copper-induced hepatotoxicity in chicken hepatocytes occurs via microRNA-12294-5p-mediated CISD1 inhibition 4, while alcohol-induced liver disease involves loss of GCN5L1-dependent CISD1 acetylation 5. In cancer, CISD1 overexpression predicts poor prognosis in gastric cancer and correlates with reduced progesterone sensitivity in endometrial cancer 6, 7. CISD1 reduction also exacerbates atherosclerosis progression by promoting ferroptosis in vascular endothelial cells 8.