In conclusion, by identifying SPARCL1 as an EC and pericyte-derived NF-κB activator promoting AT2 cell differentiation, as well as an NF-κB-dependent transcriptional program in AT2 cells, our study advances the understanding of the roles of NF-κB in lung development, with significant implications for both neonatal and chronic lung diseases. This evidence concerns the gene SPARCL1 and chronic lung disease.