Remarkably, mutations underlying monogenetic obesity in humans have been identified not only in the POMC/MC4R genes, but also in transcription factors and neurotransmitters that modulate the activity of the homeostatic melanocortin circuitry, such as single-minded homolog 1 (SIM1) (Bonnefond et al., 2013; Ramachandrappa et al., 2013), brain-derived neurotrophic factor (BDNF) (Gray et al., 2006; Han et al., 2008, Xu et al., 2003) and tyrosine receptor kinase B (encoded by NTRK2) (Yeo et al., 2004), highlighting their important role in the physiological regulation of energy homeostasis. Here, SIM1 is linked to obesity disorder.