In this issue of Blood, Yi et al reveal an important role for the protein phosphatase Wip1 (PPM1D) in the regulation of B-cell homeostasis.(1) Mice deficient in the Wip1 gene display increased apoptosis in the pre-B-cell compartment and a reduction in peripheral B-cell numbers, a phenotype exacerbated with age and upon serial transplantations of bone marrow (BM) cells. 1 Even though Wip1 has the ability to modulate multiple signaling pathways in the cell, the restoration of B-cell numbers upon deletion of the p53 gene(1) suggests that an autoregulatory loop between p53 and Wip1 is of importance to maintain normal production of B lymphocytes.