RAI1’s regulation of BDNF in the hypothalamus may contribute to the hyperphagia and obesity seen in Smith–Magenis syndrome (Burns et al. 2010) and haploinsufficiency of RAI1 results in abnormal expression of a number of genes associated with obesity, including proopiomelanocortin (POMC). Here, POMC is linked to obesity due to melanocortin 4 receptor deficiency.