Cathepsin K (catK), a lysosomal cysteine protease, exerts strong elastinolytic and collagenolytic activity and is implicated in a range of pathological disorders including cardiovascular disease. CatK expression was found to be elevated in human aortic aneurysm pointing to a role in this vasculopathy. In the angiotensin II (Ang II)-induced mouse model for aneurysm formation, catK, S and C expression was strongly upregulated. Therefore, we investigated the effect of catK deficiency on Ang II-induced aneurysm formation in the abdominal aorta of apoE−/− mice.Contrary to our expectations, catK deficiency did not protect against aneurysm formation, nor did it affect medial elastin breaks. Proteolytic activity in abdominal aortic lysates were comparable between apoE−/− and catK−//−apoE−/− mice. Adventitial presence of catS- and catC-expressing cells was significantly increased in catK−/−//apoE−/− versus apoE−/− mice, which might have compensated for the deficiency of catK-derived proteolysis in the aneurysm tissue of catK deficient apoE−/− mice. Circulating granulocytes and activated T cell numbers were significantly increased in Ang II-infused catK−/−//apoE−/− mice, which is consistent with the borderline significant increase in adventitial leukocyte content in catK−/−//apoE−/− compared to apoE−/− mice. Strikingly, despite unchanged proteolytic activity in AAA lesions, collagen content in the aneurysm was significantly increased in catK−//−apoE−/− mice. In conclusion, while catK deficiency has major impact on various vasculopathies, it did not affect murine aneurysm formation.