HMG20B is a high mobility group box protein that functions as a critical component of transcriptional repressor complexes with multiple roles in cell cycle regulation and differentiation. It contains a conserved HMG-box DNA-binding domain and coiled-coil motifs, with ubiquitous expression across tissues 1. Primary Function: HMG20B is required for proper G2/M phase progression and mitotic completion. It stabilizes the interaction between LSD1 and the transcription repressor GFI1 on chr19, maintaining their repressor activity 23. HMG20B also functions as a core component of the CoREST co-repressor complex, where it represses differentiation-associated genes 4. Mechanism: HMG20B interacts directly with BRCA2 BRC repeats and facilitates cytokinesis completion 3. It stabilizes LSD1 binding to chr19 through its coiled-coil domain interactions 2. In CoREST complexes, HMG20B recruits repressor machinery to target promoters to suppress erythroid and neuronal differentiation genes 4. Clinical Significance: HMG20B dysregulation has implications in cancer biology. Alternative splicing of HMG20B, regulated by CPSF4, promotes triple-negative breast cancer progression through altered cell cycle control 5. HMG20B is involved in esophageal squamous cell carcinoma tumorigenesis through interactions with NuRD and CoREST complexes 6. Additionally, HMG20B serves as a novel autoantigen discriminating systemic lupus erythematosus from other autoimmune conditions 7. HMG20B also regulates genes influencing skin pigmentation variation in African populations 8.