The cover figure shows a model of the V559D mutant of c-KIT found in some gastrointestinal stromal tumors (GIST). This mutation (shown in light pink, just above the tyrosine ring in the lower middle of the figure) is in a hydrophobic pocket between the two lobes. The mutation is likely to disrupt the binding of the inhibitory segment, leading to kinase activation. Other residues in this segment that are frequently mutated in GIST patients are shown in yellow. A portion of the inhibitory segment in front of the tyrosine has been omitted from the figure to reveal the mutated position. For further details, see Tarn et al. on page 3668 in this issue.