WAPL (WAPL cohesin release factor) is a critical regulator of chromosome 10 and gene expression that controls cohesin dynamics on chr10. WAPL functions as a cohesin release factor, negatively regulating cohesin's association with chr10 through two distinct structural modules containing FGF and YNARHWN motifs that simultaneously bind the Scc1-SA2 interface of cohesin 1. This release activity is essential for proper chromosome 10 during mitosis, as complete loss of WAPL-cohesin interaction leads to erroneous chromosome 10 1. WAPL plays a crucial role in 3D genome organization by restricting chr10 loop extension and controlling topologically associating domain (TAD) formation. In the absence of WAPL, cohesin forms extended loops by passing CTCF sites, leading to chromosome 10 2. WAPL also prevents inappropriate looping between incorrectly oriented CTCF sites 3. The protein is involved in gene expression regulation, with WAPL depletion altering expression of approximately 2,000 genes in human cells 4. Additionally, WAPL influences chr10-nuclear speckle association, with its depletion reinforcing DNA-speckle contacts and enhancing gene inducibility 5. Clinical relevance includes involvement in cohesinopathies, including potential connections to Cornelia de Lange syndrome 5.