Neutrophils play a key role in the innate immune system and represent the body's primary line of defense against invading pathogens, while the activation of neutrophils is also critically involved in tissue damages. Thus, properly controlling the development, homeostasis, and functional activities of neutrophils is very important. However, the molecular mechanisms that accomplish this balanced effect remain poorly understood. Wild-type (WT) p53-induced phosphatase 1 (Wip1, also called PP2Cδ) is a serine/threonine protein phosphatase belonging to the type 2Cδ protein phosphatases.It is overexpressed in many cancers and recognized as a novel oncogene inhibiting several p53-dependent tumor suppressor pathways.Therefore, Wip1 is thought to be a promising drug target for cancer therapy. Recent collaborative studies of Zhao Yong’s group in institute of Zoology, Chinese Academy of Sciences and Zhang Lianfeng’s group in Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences demonstrate that the phosphatase Wip1 is an intrinsic-negative master for neutrophil development. Wip1 is selectively expressed in resting neutrophils among all immune cells and is up-regulated gradually during neutrophil maturation.Wip1-deficient mice displayed neutrophilia with significantly expanded granulocytic differentiation and hypermaturation phenotype in a cell-intrinsic and specific manner. Further molecular studies showed that wip1 negatively modulates the neutrophil differentiation process and maturation state from its progenitor cells through p38 MAPK-STAT1-C/EBPα pathway. Wip1, as the phosphatase identified to be an intrinsic-negative master for neutrophils, may be a promising target for therapeutic intervention to modulate neutrophil function in its related diseases.