Reduced KLB expression has been suggested to play a role in a concept called FGF21 resistance, a pathophysiological state in rodents and humans with obesity associated with increased plasma FGF21 levels, reduced KLB/FGFR expression, or a reduced response to exogenously administered FGF21 (46, 59–61). The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.