Connective tissue insufficiency can be either caused by genetic defects as observed in alpha-1 anti-trypsin deficiency (a well established genetically determined form of COPD/emphysema where elastin decrease can be directly related to the observed alveolar dilation, loss of elastic recoil and airflow obstruction), or it may be ascribed to ill defined causes inducing mesenchymal precursor cell senescence and progressive decrease of matrix protein production, as suggested in this review. The gene discussed is ELN; the disease is chronic obstructive pulmonary disease.