Using single-cell RNA sequencing, the authors identified novel markers of smooth muscle cell phenotype modulation during aortic aneurysm development, including enhanced TGF-β signaling and Kruppel-like factor 4 (Klf4) overexpression, confirming their observations of the Fbn1C1041G/+ MFS mouse model. Here, KLF4 is linked to aortic aneurysm.