TRPM6

TRPM6, short for transient receptor potential cation channel subfamily M member 6, is a member of the TRP ion channel family. It functions as a Mg2+-permeable cation channel and is considered a channel-kinase, containing an intracellular kinase-like domain at its C-terminus.

In humans, TRPM6 is predominantly expressed in epithelial tissues such as the intestine and kidney, especially in intestinal enterocytes and distal convoluted tubule cells. The channel participates in active apical magnesium uptake in the intestine and contributes to magnesium reabsorption in the kidney, playing a key role in whole-body Mg2+ homeostasis. TRPM6 can form functional channels as a homomultimer and, in some tissues, can co-assemble with TRPM7 to create heteromeric channels, which can influence channel activity, trafficking, and regulation.

Regulation of TRPM6 involves intracellular Mg2+ levels and interactions with other proteins; it is influenced by cellular signaling mechanisms that affect channel trafficking and surface expression. The TRPM6/TRPM7 axis is part of a broader mechanism for maintaining magnesium balance, and disruption of this system can impact Mg2+ uptake and homeostasis.

Clinical significance: Mutations in TRPM6 cause autosomal recessive hypomagnesemia with secondary hypocalcemia (HSH). Affected individuals exhibit low serum Mg2+, neuromuscular symptoms such as seizures, and hypocalcemia due to impaired magnesium signaling. Management typically includes high-dose magnesium supplementation, often initiated in infancy or early childhood. The condition highlights the essential role of TRPM6 in intestinal magnesium absorption and renal magnesium reabsorption.

See also TRPM7 for related channel-kinase functions and potential compensatory interactions.