[5] ADAR enzymes bind to double-stranded RNA (dsRNA) and convert adenosine to inosine (hypoxanthine) by deamination.

Recent research supports a linkage between RNA-editing and nervous system disorders such as amyotrophic lateral sclerosis (ALS).

Atypical RNA editing linked to ADAR may also correlate to mental disorders such as schizophrenia, epilepsy, and suicidal depression.

[13] The ADAR enzyme and its associated gene were discovered accidentally in 1987 as a result of research by Brenda Bass and Harold Weintraub.

[14] These researchers were using antisense RNA inhibition to determine which genes play a key role in the development of Xenopus laevis embryos.

Recently, ADARs have also been discovered as a regulator on splicing and circRNA biogenesis with their editing capability or RNA binding function.

[17][18][19] It is believed that ADAR evolved from ADAT (Adenosine Deaminase Acting on tRNA), a critical protein present in all eukaryotes, early in the metazoan period through the addition of a dsRNA binding domain.

This, along with its presence in the majority of modern phyla, indicates that RNA editing is essential in regulating genes for metazoan organisms.

ADARs are suggested to have two functions: to increase diversity of the proteome by inducing creation of harmless non-genomically encoded proteins, and protecting crucial translational sites.

A hydrated intermediate will exist for a short period of time, then the amine group will leave as an ammonia ion.

[26] Aicardi–Goutières syndrome is a genetic inflammatory disease primarily affecting the skin and the brain and it is characterized by high levels of IFN-α in cerebral spinal fluid.

[28] This buildup of dsRNA stimulates IFN production without a viral infection, causing an inflammatory reaction and autoimmune response.

[30] In humans, the P193A mutation in the Zα domain is causal for Aicardi–Goutières syndrome[26] and for the more severe phenotype found in Bilateral Striatal Necrosis/Dystonia.

[32] In motor neurons, the most well-grounded marker of amyotrophic lateral sclerosis (ALS) is the TAR DNA-binding protein (TDP-43).

When there is failure of RNA-editing due to downregulation of TDP-43, motor neurons devoid of ADAR2 enzymes express unregulated, leading to abnormally permeable Ca2+ channels.

Editing mRNA typically imparts missense mutations leading to alterations in the beginning and terminating regions of translation.

Researchers observed high levels of oncogenetic A-to-I editing in circular RNA precursors, directly confirming ADAR's relationship to cancer.

Results suggest the irregular regulation is responsible for the disrupted A to I editing pattern seen in HCC and that ADAR1 acts as an oncogene in this context whilst ADAR2 has tumor suppressor activities.

[36] ADAR1 may be downregulated by cAMP- response element binding protein (CREB), limiting its ability to act on miRNA.

Research on measles virus shows ADAR1 enhancing viral replication through two different mechanisms: RNA editing and inhibition of dsRNA-activated protein kinase (PKR).