Besides genetic defects and pharmacological interventions to inhibit glucagon signaling, hepatic disorders (e.g., NAFLD and NASH (9, 22, 23)) and certain metabolic conditions (e.g., obesity (24, 25), T2DM (22)) have been associated with impaired glucagon signaling and hence disrupted LACA (26, 27). The gene discussed is GCG; the disease is obesity due to melanocortin 4 receptor deficiency.