HSPB6 (heat shock protein family B member 6) is a 17-kDa small heat shock protein that functions as a molecular chaperone, maintaining denatured proteins in a folding-competent state 1. Unlike other small heat shock proteins that form large oligomers, HSPB6 exists predominantly as dimers in solution while retaining comparable chaperone activity to other family members 12. The protein is highly and constitutively expressed in muscular tissues including smooth, cardiac, and skeletal muscle, where it plays crucial roles in muscle function 34. HSPB6 mediates cardioprotective signaling and protects against stress-induced cellular damage 14. Its protective mechanism involves interaction with BECN1 to regulate autophagy flux, with mutations like S10F causing dilated cardiomyopathy through impaired BECN1 binding and reduced autophagy 5. The protein also interacts with 14-3-3ζ in a phosphorylation-dependent manner, forming 1:1 complexes that may regulate various cellular processes 6. Recent studies have identified HSPB6 variants as causes of late-onset distal myopathy 7, and overexpression shows anti-cancer effects in osteosarcoma through ERK signaling pathway inhibition 8. The protein's versatility stems from its ability to regulate diverse client proteins and form heterooligomers with other small heat shock proteins.