Although we cannot exclude an uncoupling of adiposity and metabolic dysfunction, considering the large body of evidence linking adipose tissue excess and/or dysfunction to metabolic disease coupled with the deleterious metabolic effects of compound Ube2e2/Ube2e1 heterozygous loss of function, the Ube2e2-null phenotype of increased adiposity is more likely to be pathological rather than metabolically benign. The gene discussed is UBE2E1; the disease is metabolic disease.