These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system.

This gene encodes the α2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of translation.

A polymorphic variant of the α2B subtype, which lacks 3 glutamic acids from a glutamic acid repeat element, was identified to have decreased G protein-coupled receptor kinase-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced basal metabolic rate in obese subjects and may therefore contribute to the pathogenesis of obesity.

Comparative analysis of the primary protein sequence of ADRA2B across placentals also showed the high conservation of residues thought to be involved in agonist binding and in G protein–coupling.

However, great variations are observed in the very long, third intracellular loop, with a polyglutamyl domain displaying pervasive length differences.