A recent study demonstrated elevated expression of the ubiquitin/ISG15-conjugating enzyme UBE2L6 in white adipose tissue from obese mice and humans; moreover, HFD-fed mice with adipose tissue-specific Ube2l6 ablation had a reduced content of subcutaneous and visceral white adipose tissue, as well as attenuated glucose intolerance, insulin resistance, compensatory hyperinsulinemia, hypercholesterolemia, and hepatic steatosis (Wei et al., 2021). The gene discussed is UBE2L6; the disease is Insulin resistance.