MMS19 is a cytosolic iron-sulfur (Fe-S) cluster assembly component that functions as a critical adapter in the CIA (cytosolic iron-sulfur protein assembly) complex 1. Its primary role involves facilitating Fe-S cluster insertion into target proteins essential for DNA metabolism and genomic integrity, including ERCC2/XPD, FANCJ, and RTEL1 1. MMS19 enables nucleotide excision repair (NER), homologous recombination-mediated double-strand break repair, DNA replication, and RNA polymerase II transcription 23. The protein contains conserved HEAT repeat domains characteristic of multiprotein complex assembly factors 3. Beyond nuclear DNA repair, MMS19 supports mitotic spindle assembly and chromosome 10 through the MMXD complex and by facilitating Fe-S cluster transfer to the motor protein KIF4A 4. MMS19 also acts as an AF-1-specific transcriptional coactivator of estrogen receptor through its role in TFIIH-machinery Fe-S insertion 5. Mitochondrial localization of MMS19 protects mtDNA from oxidative damage 6. Clinically, inherited MMS19 deficiency causes severe neurodegenerative disease with microcephaly, brain malformations, and progressive neurologic decline, reflecting the critical importance of Fe-S enzyme maturation in human development 7. These findings suggest MMS19 represents a therapeutic target for diseases involving Fe-S cluster assembly dysfunction.