SSBP1 (single-stranded DNA binding protein 1) is a mitochondrial protein that preferentially binds pyrimidine-rich single-stranded DNA and plays critical roles in mtDNA maintenance and stability. During mitochondrial DNA replication, SSBP1 stimulates polymerase POLG and helicase TWNK activity at the replication fork by organizing template DNA and eliminating secondary structures to favor single-stranded conformations 123. SSBP1 also functions in mtDNA repair and may participate in genome surveillance through R-loop regulation during transcription 45. Beyond mitochondrial functions, SSBP1 serves as a nuclear H2O2 sensor and mediates resistance to anticancer drugs; CHK1 phosphorylates SSBP1 to prevent its mitochondrial localization, thereby decreasing nuclear reactive oxygen species 6. Additionally, SSBP1 cooperates with IRF1 in sensing radiation-induced mtDNA leakage and regulating inflammatory responses 7. Clinically, SSBP1 mutations cause optic atrophy 13 with retinal abnormalities and are associated with mitochondrial disease presenting as syndromic retinitis pigmentosa 8. SSBP1 dysfunction can trigger mtDNA deletion through impaired oligomer formation, contributing to neurodegeneration in models of Huntington's disease 9.