Schematic of normal hematopoietic development of the eosinophil granulocyte and impact of knocking out genes encoding the two most abundant eosinophil secondary granule proteins. EoPs, defined by expression of a high-affinity receptor for IL-5 (IL-5Rα), develop from common myeloid progenitors (CMPs) in humans and from GMPs in the mouse. Double deletion (knockout) of the murine genes encoding eosinophil granule MBP-1 and EPX (MBP-1^−/−/EPX^−/−) leads to impaired development of eosinophil secondary granules (defective granulogenesis) in EoPs, inducing programmed cell death (apoptosis) and a consequent profound eosinophil deficiency in these mice. The results of the study by Doyle et al¹  suggest that normal granulogenesis may be a novel checkpoint for successful eosinophil differentiation, such that defective granulogenesis leads to impaired survival (apoptosis) of developing eosinophils, or that loss of expression of MBP-1 and EPX disrupts lineage-instructive gene regulatory mechanisms affecting continued EoP self-renewal and/or survival. Baso, basophil; EARs, eosinophil-associated ribonucleases; HSC, hematopoietic stem cell; Mac, monocyte/macrophage; MPP, multi-potential progenitor; PMN, polymorphonuclear neutrophil; RIP, rest in peace.