The multiple functions of the co-chaperone stress inducible protein 1

[Display omitted] •STI1 is a co-chaperone involved in the correct client proteins' folding.•Extracellular STI1 is crucial for CNS maintenance and homeostasis.•STI1 expression is associated with tumor progression and impaired survival of patients.•STI1 can be a biomarker and therapeutic target for several malignancies. Stress inducible protein 1 (STI1) is a co-chaperone acting with Hsp70 and Hsp90 for the correct client proteins’ folding and therefore for the maintenance of cellular homeostasis. Besides being expressed in the cytosol, STI1 can also be found both in the cell membrane and the extracellular medium playing several relevant roles in the central nervous system (CNS) and tumor microenvironment. During CNS development, in association with cellular prion protein (PrPc), STI1 regulates crucial events such as neuroprotection, neuritogenesis, astrocyte differentiation and survival. In cancer, STI1 is involved with tumor growth and invasion, is undoubtedly a pro-tumor factor, being considered as a biomarker and possibly therapeutic target for several malignancies. In this review, we discuss current knowledge and new findings on STI1 function as well as its role in tissue homeostasis, CNS and tumor progression.