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These proteins share a CDGSH motif and redox\u2010active [2Fe\u20102S] clusters. MitoNEET (CDGSH iron\u2013sulfur domain\u2010containing protein 1) is an outer mitochondrial membrane protein that was recently discovered as an off\u2010target of the antidiabetic drug pioglitazone, and plays an essential role in mitochondrial bioenergetics, mitophagy, and iron metabolism. CDGSH iron\u2013sulfur domain\u2010containing protein 2 (nutrient\u2010deprivation autophagy factor 1) is located on the endoplasmic reticulum and is found to be antiaging and associated with Wolfram Syndrome 2, while CDGSH iron\u2013sulfur domain\u2010containing protein 3 (mitochondrial inner NEET protein) is present in the mitochondrial matrix. In this review, we will evaluate the state of the field in the development of NEET protein interacting ligands, which can serve as pharmacological tools to study the biology\/biochemistry of NEET family proteins in disease. 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