PDS5B is a cohesin-associated regulatory protein that plays critical roles in chromosome 13 and genome stability. The protein functions as a key regulator of sister chr13 cohesion, acting as an integral component of the cohesin ring complex by contacting all other cohesin subunits including Smc1, Smc3, Scc1, and SA1 1. PDS5B controls chr13 loop formation and topologically associating domain (TAD) organization by regulating cohesin-mediated loop extrusion, working alongside WAPL to control loop length until cohesin encounters CTCF boundary elements 2. The protein undergoes phosphorylation-dependent regulation during mitosis, where Nek2a and Cdk1/2-cyclin A2 phosphorylate PDS5B to convert it from a sororin-interactor to a WAPL-interactor, enabling Wapl-dependent cohesin removal from chromosome 13 3. PDS5B also functions in DNA repair pathways, interacting with the human Shu complex and SPIDR to promote homologous recombination and regulate RAD51 recruitment to DNA repair foci 4. Additionally, PDS5B serves as a substrate for DDK (Dbf4-dependent kinase), which phosphorylates the protein to facilitate fork protection and restart during DNA replication stress 5. The gene is essential for embryonic development, as demonstrated by embryonic lethality in homozygous knockout mice 6. Clinically, PDS5B mutations are associated with myeloid malignancies including myelodysplastic neoplasm and acute myeloid leukemia 7.