Phosphatases fine-tune signaling thresholds in feedback loops and pathway crosstalk which enables them to control various pathological processes such as tumor immune evasion and metabolic diseases along with inflammation, fibrosis and neurodegeneration. PTP1B is a prototypical dual target in metabolic disease and oncology, SHP2 (PTPN11) has emerged as an oncotarget and master node of the RAS/MAPK pathway, and PTEN is the archetypal tumor suppressor. In all, phosphatases have recently emerged as a set of interesting drug targets, with drugs in various stages of development, including inhibitors, allosteric modulators, reversible and irreversible covalent inhibitors, and even targeted protein degraders (e.g., molecular glue or PROTAC approaches).
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