TRPV6

TRPV6, or transient receptor potential vanilloid 6, is a calcium-permeable ion channel of the TRPV subfamily. It forms functional tetramers in the plasma membrane and shows high selectivity for Ca2+. In humans, TRPV6 is predominantly expressed in the apical membrane of enterocytes in the small intestine, where it contributes to dietary calcium absorption, and is also detected in the kidney and several reproductive tissues.

Function and mechanism: TRPV6 mediates apical Ca2+ entry into intestinal epithelial cells and couples to intracellular calcium-binding proteins, such as calbindin-D9k, and to the basolateral Ca2+-export pump PMCA1b, facilitating transepithelial calcium transport. This arrangement supports the uptake of dietary calcium into the circulation.

Regulation: Expression of TRPV6 is upregulated by 1,25-dihydroxyvitamin D3 via the vitamin D receptor, which coordinates transcription of calcium-regulating proteins to support intestinal calcium uptake. The channel is a constitutively Ca2+-permeable pore and can be modulated by intracellular Ca2+/calmodulin and by extracellular calcium levels; several pharmacological agents can inhibit or modify its activity.

Clinical significance: Altered TRPV6 expression has been reported in several cancers, including prostate and breast cancer, where it may contribute to cell proliferation and invasion. Because of its role in calcium homeostasis and its cancer associations, TRPV6 is studied as a potential biomarker and therapeutic target, with research evaluating inhibitors and gene-silencing approaches in preclinical models.