Key differences include their (i) cellular origins—MMP-12 is primarily synthesized by macrophages while MMP-9 is produced in significant amounts by a variety of cell types; (ii) substrate specificity—MMP-12 has a pronounced affinity for elastin, while MMP-9 can also degrade some collagens and gelatin; and (iii) roles in COPD pathogenesis—MMP-12 is prominently implicated in emphysema formation, while both MMPs participate in the regulation of inflammation. This evidence concerns the gene MMP12 and pulmonary emphysema.