Phosphofructokinase (PFK) is the enzyme that catalyses the committed, rate-limiting step of glycolysis: the transfer of a phosphate group from ATP to fructose-6-phosphate, forming fructose-1,6-bisphosphate. This reaction is the principal control point of carbohydrate breakdown, and PFK is exquisitely regulated, activated by ADP and fructose-2,6-bisphosphate when energy is needed, inhibited by ATP and citrate when energy is abundant. Through this single enzyme, the cell matches glucose burning to its energy status moment by moment. In nutrition and exercise physiology, PFK regulation explains metabolic flexibility: the shift between carbohydrate and fat oxidation with fasting, feeding, and training intensity runs through control points like this one. Defects in muscle PFK cause glycogen storage disease type VII, with exercise intolerance and cramps.