Given that the general CRL inhibitor MLN4924 efficiently inhibits hyperinsulinemia, but not normal insulin levels or sensitivity, and that CRL4COP1 is particularly sensitive to partial disruption of CSN regulation, more specific modulation of insulin secretion via targeting Cul4 regulators that determine CRL4COP1 assembly, including the inositol polyphosphate pathway, may benefit obese and early T2D patients. Here, IL31RA is linked to Hyperinsulinemia.