To elucidate the underlying cellular mechanisms, functional effects of mutations and polymorphisms that were linked to the development of obesity were investigated. The sequence alterations of interests were described to potentially interfere with the post-translational processing of CART, leading to defective protein biosynthesis and deranged cellular distribution of the peptide, while modulation in the nuclear protein binding affinity was also reported to attenuate biological activity. Despite the plausible challenges imposed on the translatability of principal observations from animal models to the less well-documented human system, aberrations in CART have been demonstrated in human studies to promote positive energy balance, endorsing a primary anorectic role of CART.