In mouse models, loss-of-function mutations in Mgrn1 lead to severe phenotypes, including left–right patterning defects, congenital heart malformations, embryonic lethality, craniofacial abnormalities, pigmentation defects, late-onset spongiform neurodegeneration, mitochondrial dysfunction and partial suppression of diet-induced obesity (Bagher et al., 2006; Cota et al., 2006; Groza et al., 2023; Gunn et al., 2013, 2019; He et al., 2003; Jiao et al., 2009b; Kong et al., 2020; Miller et al., 1997; Mukherjee and Chakrabarti, 2016b; Overton and Leibel, 2011; Phan et al., 2002; Sun et al., 2007). Here, MGRN1 is linked to obesity due to melanocortin 4 receptor deficiency.