(A) In the adult proximal or bronchiolar epithelium, cells expressing Sox2, p63, and Krt5 are thought to be progenitors capable of regenerating injured or denuded airway epithelium. Whether these markers denote unique, distinct, or overlapping progenitor populations is unknown, but data show that p63 and Krt5 mark a more proximal population of cells than Sox2 alone, which is expressed throughout tracheal and bronchiolar regions (15, 70). Notch signaling is known to regulate the decision to generate secretory lineages (i.e., Scgb1a1⁺) versus neuroendocrine cells within the proximal airways. The secretory lineage has also been shown to generate both ciliated epithelium (β-tubulin IV⁺) as well as goblet cells (Muc5A/C⁺) after injury to the bronchiolar epithelium. (B) In the alveolar epithelium, less is known about the relationship between the two major cell types, AEC1 and AEC2 cells. There is some in vitro evidence that AEC2 cells can act as progenitors to repopulate lost AEC1 and AEC2 cells after injury (63). Additional genetic and molecular data are needed to assess whether there is a resident alveolar progenitor or whether AEC2 cells are facultative progenitors. Aqp5, aquaporin 5; CGRP, Calcitonin gene–related peptide; Pgp9.5, protein gene product 9.5; T1α, podoplanin.