KITLG

KIT ligand (KITLG), also known as stem cell factor (SCF), is a cytokine encoded by the KITLG gene in humans. The protein binds to the KIT receptor (CD117), a receptor tyrosine kinase, and promotes survival, proliferation, and differentiation of multiple cell lineages. KITLG exists in two main forms: a membrane-bound form and a soluble form generated by proteolytic processing; both forms can activate KIT signaling and influence target cells.

KITLG plays essential roles in hematopoiesis, melanogenesis, and germ cell development. It supports hematopoietic stem and progenitor cells, promotes melanocyte survival and maturation, and is important for primordial germ cell maintenance and migration during development. It also contributes to mast cell development and function. Upon KIT binding, KITLG triggers downstream signaling pathways such as PI3K/AKT and MAPK/ERK, which regulate cell survival, proliferation, and migration.

Expression of KITLG is widespread in mesenchymal and stromal tissues, including bone marrow, skin, and gonadal environments, with regulation by developmental cues and physiological conditions. The KIT-KITLG signaling axis integrates signals from the microenvironment to influence cell fate decisions.

Clinical relevance includes involvement in disorders related to KIT signaling. Alterations in KITLG or KIT signaling can contribute to pigmentary abnormalities and impact germ cell development. Genome-wide association studies have linked KITLG variants to susceptibility to certain cancers, including testicular germ cell tumors, and to human pigmentation traits such as hair color. KITLG remains a focus of research into hematopoietic, reproductive, and pigmentary biology.