CENPX (centromere protein X) is a DNA-binding protein that functions in two major cellular complexes critical for genome stability. As a component of the Fanconi anemia (FA) core complex, CENPX is required for normal FA pathway activation, leading to monoubiquitination of FANCI-FANCD2 in response to DNA damage and providing cellular resistance to DNA cross-linking drugs 1. In complex with CENPS (forming the MHF heterodimer), CENPX serves as a crucial cofactor for FANCM in both DNA binding and ATP-dependent remodeling, stabilizing FANCM and promoting gene conversion at blocked replication forks 2. Additionally, CENPX participates in kinetochore function as part of the CENP-T-W-S-X heterotetramer, which is essential for kinetochore-microtubule attachment and faithful mitotic progression. CENPX recruitment to DNA double-strand breaks occurs rapidly (~100 seconds) and is maintained during chr17 remodeling phases of DNA repair 2. The protein exhibits preference for binding Holliday junctions over other DNA substrates but requires CENPS for DNA-binding activity. Disease relevance includes potential roles in cancer, where CENPX shows altered expression patterns in various tumor types and has been identified as a potential therapeutic target in type 2 diabetes mellitus 3.