RSPO1 is a secretory protein that plays determinant roles in intestinal organoid growth[21] and female sex determination.[22] To further examine the biological function of RSPO1 in obesity, we first analyzed RSPO1 expression using online microarray data across various organs and cell lines.[23] We found that RSPO1, but not other RSPO members (RSPO2–4), was specifically and highly expressed in WAT (Figure 1B). Here, RSPO2 is linked to obesity due to melanocortin 4 receptor deficiency.