CIAO2A (also known as FAM96A) is a component of the cytosolic iron-sulfur protein assembly (CIA) machinery that mediates the incorporation of iron-sulfur clusters into extramitochondrial Fe/S proteins 1. As part of the CIA complex, CIAO2A collaborates with CIAO1 to specifically mature aconitase (ACO1) and stabilize iron regulatory protein 2 (IREB2), thereby linking cytosolic iron-sulfur protein maturation with cellular iron regulation 1. The CIAO2A-CIAO1 complex can bind [4Fe-4S] clusters via cysteine residue 90 of CIAO2A and transfer these clusters to apo-IRP1 to generate active aconitase 2. Recent studies reveal CIAO2A can also recognize client proteins bearing C-terminal targeting complex recognition (TCR) motifs, suggesting a broader role in iron-sulfur protein maturation than previously appreciated 3. Beyond iron homeostasis, CIAO2A functions as a pro-apoptotic protein through interaction with APAF1 and serves as a tumor suppressor, with reduced expression observed in gastrointestinal stromal tumors 4. CIAO2A also regulates macrophage polarization and metabolic homeostasis, with deficiency promoting M2 macrophage polarization and protecting against sepsis 5. The protein plays critical roles in adipose tissue homeostasis and energy balance through regulation of mTOR signaling and mitochondrial function 6.