The potential functions of BEST4+ cells (cGMP signaling, pH regulation, electrolyte and fluid transport, and antimicrobial defenses) suggest that they may be central in epithelial homeostasis and that they could be potentially involved in multiple diseases including IBD, visceral pain, diarrheal diseases, cystic fibrosis, and obesity (7, 25, 49). Here, BEST4 is linked to obesity due to melanocortin 4 receptor deficiency.