ADA2 and immunodeficiency disease: Humans have two ADA enzymes: ADA2 has a signal sequence and is responsible for most of the extracellular activity, while ADA1 lacks a signal sequence and is responsible for most of the intracellular activity.[78, 79] Mutations in ADA1, ADA2, and PNP salvage enzymes lead to complex syndromes in humans that include features of immunodeficiencies coupled with auto‐inflammation.[80, 81, 82]