Accordingly, strategies to restore hepatic ER Ca2+ levels, such as overexpression of SERCA or suppression of IP3R, improve ER function and promote metabolic homeostasis in mouse models of obesity (Arruda et al., 2014; Feriod et al., 2017; Fu et al., 2011; Wang et al., 2012). Here, ITPR1 is linked to obesity due to melanocortin 4 receptor deficiency.