The present study aimed to determine the requirement of PLD activity for Golgi/TGN retention of KITmut in GIST cells by investigating the relationship between the PLCγ2–PKD2 pathway and PLDs using PLD inhibitors, knockdown experiments, immunofluorescence confocal microscopic analysis, and biochemical assays. Here, PLCG2 is linked to gastrointestinal stromal tumor.