Forkhead box protein K1 (FOXK1)

Forkhead box protein K1 (FOXK1) is a transcription factor belonging to the forkhead box family, encoded by the FOXK1 gene. It plays a central role in regulating cellular metabolism, particularly by promoting aerobic glycolysis—a process where glucose is converted to lactate even when oxygen is present. This metabolic reprogramming supports rapid cell growth and proliferation, which occurs during embryogenesis, immune cell activation, and tumor development. Mechanistically, FOXK1 upregulates key glycolytic enzymes such as hexokinase‑2, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase while suppressing mitochondrial oxidation of pyruvate through increased expression of pyruvate dehydrogenase kinases. Additionally, it acts as a negative regulator of autophagy in skeletal muscle under starvation conditions by repressing autophagy gene expression. Dysregulation or overexpression of FOXK1 has been implicated in various diseases including cancer (notably breast cancer), genetic syndromes like Bainbridge-Ropers syndrome, certain neuropathies, and chronic kidney disease due to its impact on cellular energy balance and proliferation.

Other names

FOXK1Forkhead box K1Forkhead box protein FOXK1