Hspb6, also known as P20/HSP20, is a 17-kDa protein belonging to the small heat shock protein family. It is ubiquitously expressed, with high levels in muscular tissues. Functioning as a molecular chaperone, Hspb6 can form dimers in solution, unlike many other sHSP family members. It is involved in diverse physiological processes such as smooth muscle relaxation, platelet aggregation, and is a key mediator in cardioprotective signaling [2].

In an Hspb6-knockout mouse model, compared to wild-type mice, there was increased mortality and a higher probability of ascending aortic dissection. Hspb6 deletion promoted vascular smooth muscle cell apoptosis, attenuated cofilin activity, leading to excessive smooth muscle cell stiffness, which eventually caused aortic dissection and rupture [1]. In cancer studies, down-regulation of Hspb6 was observed in colon cancer tissues and osteosarcoma, while its overexpression inhibited osteosarcoma cell proliferation, migration, and invasion, and induced apoptosis, potentially through the ERK signaling pathway. In prostate cancer, down-regulation of Hspb6 correlated with poor prognosis, and its activation by 8-Br-cGMP led to apoptosis in prostate cancer cells [3,4,5].

In conclusion, Hspb6 plays essential roles in muscle function and various disease conditions. Gene-knockout mouse models have revealed its significance in aortic dissection, showing that Hspb6 deficiency-induced excessive vascular smooth muscle cell stiffness is a new pathogenetic mechanism for aortic dissection. In cancer, Hspb6 seems to have an anticancer role, as its down-regulation is associated with tumor progression in some cancers, and overexpression inhibits cancer cell growth and metastasis.