The molecular genetics of α 1 antitrypsin deficiency

The human serum protein α 1 ‐antitrypsin is the major source of antiprotease activity found in the blood. The protein is synthesised primarily by liver cells but, to a lesser extent, by at least one other cell type. Expression of the gene has provided a paradigm for studies on transcriptional regulation in liver and of tissue‐specific promoter activity. The pleiomorphic nature of the gene has given rise to a variety of α 1 ‐antitrypsin variants some of which are clinically important. These abnormal variants may be poorly synthesised, rapidly degraded or inefficiently secreted; studies on the molecular mechanisms which underly these events are providing interesting insights into the general processes of protein transport and intracellular protein degradation.