In human, the expression of CART transcripts and peptides has been characterized in various hypothalamic areas involved in appetite control and lipid homeostasis. From the perspective of population genetics, genome-wide study of human obesity-susceptibility loci revealed linkage to a locus harboring the human CART gene, whereas mutation profiling has associated alterations in CART with reduced metabolic rate and resting energy expenditure, hyperphagia, obesity and elevated incidence of type II diabetes. Intriguingly, whilst a role of CART in regulating energy expenditure remains equivocal in overexpression studies and considered discordant in gene deletion approach in animal models, mutation screening in humans has consolidated the involvement of CART in the modulation of energy expenditure, body weight and dyslipidaemia.