Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder caused by mutations in the SERPINA1 gene, leading to reduced levels or dysfunctional alpha-1 antitrypsin (AAT) protein. AAT plays a crucial role in protecting the lung tissue from the damage caused by neutrophil elastase. Initially diagnosed based on electrophoretic patterns, the changes in the protein are attributed to different phenotypes that can occur in homozygous or heterozygous forms: PiZZ, PiSZ, PiSS, PiMZ, PiMS, and PiMM (wild type), in >99% of the affected. There is a broad clinical spectrum in the presentation and progression of both liver and lung disease, reflected in the huge heterogeneity of reported parameters. The basic test for AATD is the measurement of alpha-1 antitrypsin in serum with a norm of >1.1 mg/dl. The workup should also involve the assessment of organ affection, both liver and lung, to assess baseline values and guide therapeutic approaches. Being a genetic disorder with the pathophysiological mechanism involving alpha-1 antitrypsin synthesis and transport mostly in the liver, liver transplantation (LTX) is a curative (gene therapy–like) approach.