AQP9

AQP9, or aquaporin-9, is a member of the aquaporin family of membrane channel proteins that facilitate the movement of water and small solutes across the cell membrane. It is classified as an aquaglyceroporin, which means it is permeable to glycerol and other small neutral solutes in addition to water. Like other aquaporins, AQP9 monomers have six transmembrane alpha helices and two conserved NPA motifs, and they form tetramers in the plasma membrane, with each monomer contributing a distinct pore.

In humans, AQP9 is expressed in several tissues, with substantial presence in the liver where it plays a key role in glycerol uptake for energy metabolism. Additional expression has been reported in immune cells such as leukocytes and in other tissues, reflecting a range of physiological roles beyond hepatic metabolism.

Functionally, AQP9 facilitates the transport of glycerol into hepatocytes, enabling glycerol to feed into gluconeogenesis or glycolysis. Water transport via AQP9 also contributes to osmotic balance, making the protein a functional link between water homeostasis and energy metabolism. Its glycerol permeability classifies it among the aquaglyceroporins, alongside other family members that regulate glycerol flux in metabolic tissues.

Regulation of AQP9 expression is linked to metabolic state. Hepatic AQP9 levels increase during fasting to accommodate heightened glycerol uptake from adipose tissue, while insulin signaling can suppress its expression. This regulatory pattern supports the liver’s role in maintaining glucose homeostasis during energy scarcity.

Clinical relevance and research perspectives focus on AQP9 as a potential target for metabolic disorders, such as obesity and type 2 diabetes, where modulating hepatic glycerol uptake could influence energy balance. It is also studied for its possible involvement in inflammatory processes in leukocytes.