Localization of ILDR2 in the ER membrane, up-regulation of ER stress markers in the livers of ADOX mice and down-regulation in ADKD mice, along with the emerging relationship between hepatic lipid accumulation and ER stress in several metabolic disorders, including obesity, hepatic steatosis and type II diabetes [16], [31], [50], suggest that ILDR2 might have a role in cellular ER stress responses. Here, ILDR2 is linked to obesity due to melanocortin 4 receptor deficiency.