The transient conditional depletion of Runx2 in the aVICs and sinus wall cells of LDLr−/−ApoB100 CAVD mice early in disease led to a significant reduction in the aortic peak velocity, mean velocity, and mean gradient, suggesting the causal role of Runx2 on the progression of AS. The gene discussed is RUNX2; the disease is aortic stenosis.