Abstract
Protein phosphatases play a critical role in maintaining immune homeostasis by regulating various signaling pathways involved in immune cell activation, differentiation, and function. In the context of systemic autoimmune diseases, dysregulation of phosphatase activity contributes to aberrant immune responses, leading to chronic inflammation and tissue damage. This review explores the role of key phosphatases from the protein serine/threonine phosphatase and protein tyrosine phosphatase families that are implicated in systemic autoimmunity. We discuss their diverse roles in immune cell subsets, the mechanisms by which their dysregulation drives autoimmune pathogenesis, and the therapeutic potential of targeting these enzymes.