The emerging role of follistatin under stresses and its implications in diseases.

Follistatin (FST), a single-chain glycosylated protein, is expressed in various tissues. The essential biological function of FST is binding and neutralizing transforming growth factor β (TGF-β) superfamily, including activin, myostatin, and bone morphogenetic protein (BMP). Emerging evidence indicates that FST also serves as a stress responsive protein, which plays a protective role under a variety of stresses. In most cases, FST performs the protective function through its neutralization of TGF-β superfamily. However, under certain circumstances, FST translocates into the nucleus to maintain cellular homeostasis independent of its extracellular antagonism activity. This review provides integrated insight into the most recent advances in understanding the role of FST under various stresses, and the clinical implications corresponding to these findings and discusses the mechanisms to be further studied.