ADA is considered one of the key enzymes of purine metabolism. The enzyme has been found in bacteria, plants, invertebrates, vertebrates, and mammals, with high conservation of amino acid sequence. The high degree of amino acid sequence conservation suggests the crucial nature of ADA in the purine salvage pathway. Primarily, ADA in humans is involved in the development and maintenance of the immune system. However, ADA association has also been observed with epithelial cell differentiation, neurotransmission, and gestation maintenance. It has also been proposed that ADA, in addition to adenosine breakdown, stimulates release of excitatory amino acids and is necessary to the coupling of A1 adenosine receptors and heterotrimeric G proteins. Adenosine deaminase deficiency leads to pulmonary fibrosis, suggesting that chronic exposure to high levels of adenosine can exacerbate inflammation responses rather than suppressing them. It has also been recognized that AMP deaminase protein and activity is upregulated in mouse hearts that overexpress HIF-1α, which in part explains the attenuated levels of adenosine in HIF-1α expressing hearts during ischemic stress. In meiotic and post-meiotic male germ cells ADA2 regulates heterochromatin via translation of the MDC1 gene.