The biology of Kit in disease and the application of pharmacogenetics

C-kit encodes a transmembrane protein with intrinsic tyrosine kinase activity, which functions as the receptor for stem cell factor. It is expressed on a variety of cell types, including mast cells, hematopoietic progenitor cells, melanocytes, germ cells, and gastrointestinal pacemaker cells. Mutations resulting in alteration of Kit function are associated with diseases involving each of these cells. Recent development of tyrosine kinase inhibitors led to their evaluation as novel therapies for diseases associated with Kit activation. This review will discuss the pathobiology of Kit in human disease, with a particular emphasis on implications for potential targeted treatment strategies in mast cell disease.