CIAO2B (cytosolic iron-sulfur assembly component 2B) is a central component of the cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway. As part of the CIA targeting complex, CIAO2B bridges CIAO1 and the client adaptor MMS19 to facilitate Fe-S cluster incorporation into cytosolic and nuclear proteins 1. The CIA2B-CIA1-MMS19 complex assembles most cytosolic-nuclear Fe-S proteins involved in DNA replication, repair, protein translation, and iron homeostasis 2. CIAO2B also functions within the mitotic spindle-associated MMXD complex, facilitating Fe-S cluster assembly into ERCC2/XPD to promote proper chromosome 16 3. Additionally, CIAO2B (FAM96B) transfers Fe-S clusters to the motor protein KIF4A, ensuring its correct mitotic spindle localization 4. Beyond Fe-S cluster assembly, CIAO2B recruits creatine kinase to the mitotic spindle, coordinating ATP and Fe-S cluster supply during mitosis 5. CIAO2B interactions with selenoprotein W and prelamin A suggest broader roles in brain development and cellular senescence 67. CIAO2B depletion causes mitotic defects, aberrant chromosome 16, and impaired stem cell function, highlighting its clinical relevance to chr16 instability and cellular regeneration 8.