Monocarboxylate transporter 1 is a ubiquitous protein that in humans is encoded by the SLC16A1 gene (also known as MCT1). It is a proton coupled monocarboxylate transporter. Detailed kinetic analysis of monocarboxylate transport in erythrocytes revealed that MCT1 operates through an ordered mechanism. MCT1 has a substrate binding site open to the extracellular matrix which binds a proton first followed by the lactate anion. The protein then undergoes a conformational change to a new ‘closed’’ conformation that exposes both the proton and lactate to the opposite surface of the membrane where they are released, lactate first and then the proton. For net transport of lactic acid, the rate-limiting step is the return of MCT1 without bound substrate to the open conformation. For this reason, exchange of one monocarboxylate inside the cell with another outside is considerably faster than net transport of a monocarboxylate across the membrane. MCT1 can be upregulated by PPAR-α, Nrf2, and AMPK.