RAD21 is a core structural component of the cohesin complex essential for maintaining chromosome 8 and gene regulation. Functionally, RAD21 mediates sister chr8 cohesion during mitosis and meiosis by stabilizing loop domains through interaction with CTCF 1. RAD21 occupancy can be analyzed at single-cell resolution to map transcription factor binding patterns across chr8 2. Beyond canonical cohesion, RAD21 contains a speckle-targeting motif required for chr8-nuclear speckle association, which regulates gene inducibility 3. RAD21 also binds to cohesin's SA2 and SCC1 subunits, sharing this interface with SGO1 to protect centromeric cohesin during mitosis 4. Clinically, RAD21 mutations cause Cornelia de Lange Syndrome (CdLS), a developmental disorder characterized by growth retardation, limb involvement, and cardiac/gastrointestinal manifestations 56. RAD21 variants produce less severe phenotypes compared to NIPBL mutations. In cancer, RAD21 amplification promotes immune evasion in ovarian cancer by epigenetically suppressing interferon signaling through interaction with YAP/TEAD4 corepressors and the NuRD complex 7. RAD21 ablation enhanced anti-PD-1 immunotherapy efficacy, suggesting therapeutic potential. These findings establish RAD21 as critical for both normal developmental processes and disease pathogenesis.