It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus.

It was independently identified by two teams in 1997 based on its sequence similarity with agouti signalling peptide (ASIP), a protein synthesized in the skin controlling coat colour.

Its secondary structure consists mainly of random coils and β-sheets[8] that fold into an inhibitor cystine knot motif.

[13] Conversely, AgRP-secreting neurons inhibit the release of TRH from the paraventricular nucleus (PVN), which may contribute to conservation of energy in starvation.

This inverse agonism not only antagonizes the action of melanocortin agonists such as α-MSH but also further decreases the cAMP produced by the affected cells.

[21] Understanding the role AgRP plays in weight gain may assist in developing pharmaceutical models for treating obesity.

Studies suggest that systems involved in the regulation of stress response and of energy balance are highly integrated.

Loss or gain of AgRP function may result in inadequate adaptive behavioural responses to environmental events, such as stress, and have potential to contribute to the development of eating disorders.

Starvation-induced hypothalamic autophagy generates free fatty acids, which in turn regulate neuronal AgRP levels.

[23] According to Mark L. Andermann and Bradford B. Lowell: "...AgRP neurons and the wiring diagram within which they operate can be viewed as the physical embodiment of the intervening variable, hunger.

[30] Another is a satiety signal, leptin, which modulates AgRP activity through inwardly rectifying potassium channels, which alter the excitability of the neurons.