Cell differentiation occurs mostly during a specific developmental time window and is irreversible. The homeobox-containing transcription factor Prox1 is a master regulator of lymphatic endothelial cell differentiation in the embryo. A study by Johnson et al. (3282-3291) published in this issue of Genes & Development now shows that continued expression of Prox1 is required to maintain lymphatic endothelial cell identity even in adult mice. These findings indicate that Prox1 is essential for the differentiation and function of the lymphatic vasculature throughout life.