The regulation of norepinephrine (NE) levels in different brainregions plays a critical role in several therapeutically relevantcontexts, such as hypertension,2 attention-deficit/hyperactivitydisorder (ADHD),3,4 and opioid withdrawal,5,6 as well as in working memory7 and executivefunction.8 NE levels are tightly regulatedby α-2-adrenergic receptors (α2Rs), which include threesubtypes: α2A, α2B, and α2C G protein-coupled receptors(GPCRs) that couple canonically to the Gαi/o proteinto modulate the activity of adenylyl cyclase (AC) and production ofcyclic adenosine monophosphate (cAMP).9 The gene discussed is IGKV2D-29; the disease is Hypertension.