MC4R and Obesity: A number of endocrine diseases are associated to GPCR misfolding and loss-of-function of the abnormal receptor (Table 1); these include X-linked nephrogenic diabetes insipidus (misfolded human arginine-vassopresin 2 receptor; V2R) [33,34], thyroid disorders (thyroid-stimulating hormone receptor; TSHR) [35], familial hypocalciuric hypercalcemia (calcium-sensing receptor; CaSR) [36], obesity (melanocortin-3 and -4 receptors; MC3R and MC4R, respectively) [37,38,39,40], and familial glucocorticoid deficiency (melanocortin-2 receptor, MC2R or adrenocorticotropin receptor, ACTHR) [41].