HSCB (heat shock cognate B) is a mitochondrial J-type co-chaperone essential for iron-sulfur cluster biogenesis and transfer. As a cochaperone partner of mitochondrial Hsp70 (HSPA9), HSCB facilitates the assembly and delivery of [2Fe-2S] clusters to recipient proteins by binding to the scaffold protein ISCU and mediating complex formation with the cytosolic iron-sulfur assembly (CIA) targeting complex components 1. This enables iron-sulfur cluster insertion into cytoplasmic and nuclear proteins including POLD1, ELP3, DPYD, and PPAT 1. HSCB contains a conserved J-domain and a distinctive N-terminal tetracysteine metal-binding domain that coordinates zinc with high affinity, critical for protein stability and function 23. Beyond its canonical iron-sulfur function, HSCB exhibits a noncanonical role in erythropoiesis and megakaryopoiesis: phosphorylation by PI3K enables HSCB to mediate proteasomal degradation of TACC3, facilitating FOG1 nuclear translocation, a key transcription factor for these hematopoietic processes 4. Mutations in HSCB cause congenital sideroblastic anemia (CSA), with both frameshift and promoter variants reducing HSCB expression and impairing iron-sulfur cluster biogenesis, hemoglobinization, and erythropoiesis 5. These findings establish HSCB as critical for both mitochondrial iron-sulfur metabolism and hematopoietic development.