IRS2 and cancer: The R24C mutation prevents INK4-family CDK4 inhibition (23, 24); in cancers, Cdk4-R24C mutation is synergistic with loss of function of Cip/Kip inhibitors (79), suggesting that Cdk4-R24C may counteract a damaging combination of loss of cyclin D2 with gain of p27 in IRS2 null β cells.