Human NK cells arise from the HSC in the bone marrow and then progress to pro-, pre-, and immature NK cells (also referred to as stage 1, 2, and 3 NK cells, respectively). The immature NK cell transits to the peripheral lymphoid compartment secondary lymphoid tissues where CD56^bright NK cells predominate. CD56^bright NK cells are also referred to as stage 4 NK cells, and current evidence suggests that they develop in the secondary lymphoid tissues into CD56^dim mature NK cells (stage 5). Key differences between CD56^bright and CD56^dim NK cells are depicted in the schematics of these two cells. Characteristics of early-stage NK cells as well as their specific transcriptional requirements are reviewed elsewhere (18). The present work suggests a role for MCM4 in the transition of CD56^bright to CD56^dim NK cells, as evidenced by the relative absence of CD56^dim NK cells in the peripheral blood with the preservation of the CD56^bright NK cell population.