HSPB2 is a small heat shock protein functioning as a molecular chaperone with ATP-independent cytoprotective activity. As a member of the sHSP superfamily, HSPB2 maintains protein quality control through protein refolding and suppression of aggregation 1. It forms dynamic hetero-oligomeric complexes with HSPB3, with assembly plasticity mediated by flexible terminal regions that facilitate diverse protein interactions 2. HSPB2 may regulate the kinase DMPK and is involved in stress responses and apoptosis regulation. Mechanistically, HSPB2 is a direct p53 target gene that regulates cellular metabolism and reactive oxygen species levels through effects on metabolic genes including HK2, SCO2, and TIGAR 3. In cancer cells, HSPB2 activates p53 downstream targets RPRM, BAI1, and TSAP6, inhibiting pancreatic cancer proliferation 4. The HspB2:HspB3 stoichiometry determines subcellular phase behavior—affecting whether complexes remain soluble, form liquid nuclear condensates, or aggregate 5. Clinically, HSPB2 shows context-dependent roles in cancer progression. In bladder cancer, HSPB2 downregulation in early tumors predicts poor prognosis, while upregulation in advanced disease supports survival, suggesting biphasic disease stage-specific roles 6. Genome-wide association studies identify HSPB2 variants as female-specific neuroticism risk loci 7. HSPB2 mutations are associated with myopathic and neurodegenerative disorders including myotonic dystrophy, Alzheimer's disease, and hereditary cerebral hemorrhage 1.