Polyphosphate: a cellular Swiss army knife

Inorganic polyphosphate (polyP) is a ubiquitous biopolymer whose functional repertoire has rapidly expanded over the past few years. How polyP controls these seemingly unrelated functions, which range from stress resistance, motility, and DNA damage control in bacteria to blood clotting, cancer and neurodegeneration in mammals, remains largely unknown. Here, we review what is known about its synthesis and degradation pathways in mammalian cells, provide an overview over the cell compartment-specific roles of polyP, and focus on recent studies, which showed that many of polyP's activities appear to be mediated by its ability to either solubilize, scaffold, or phase separate proteins. Future studies will show how polyP achieves these vastly different effects on proteins and hence controls its many functions.