Mice with mutant carboxypeptidase E, Cpe, display endocrine disorders like obesity and infertility. In some strains of mice, the fat mutation also causes hyperproinsulinemia in adult male mice, but this is not found in all strains of mice.  The obesity and infertility in the Cpe mice develop with age; young mice ( mice is impaired, with a large accumulation of peptides with C-terminal lysine and/or arginine extensions.  Levels of the mature forms of peptides are generally reduced in these mice, but not eliminated.  It is thought that a related enzyme (carboxypeptidase D) also contributes to neuropeptide processing and gives rise to the mature peptides in the Cpe mice.
Mutations in the CPE gene are not common within the human population, but have been identified. One patient with extreme obesity (Body Mass Index >50) was found to have a mutation that deleted nearly the entire CPE gene. This patient had intellectual disability (inability to read or write) and had abnormal glucose homeostasis, similar to mice lacking CPE activity.
In obesity, high levels of circulating free fatty acids have been reported to cause a decrease in the amount of carboxypeptidase E protein in pancreatic beta-cells, leading to beta-cell dysfunction (hyperproinsulinemia) and increased beta-cell apoptosis (via an increase in ER stress).  However, because CPE is not a rate-limiting enzyme for the production of most neuropeptides and peptide hormones, it is not clear how relatively modest decreases in CPE activity can cause physiological effects.