Biochemistry and pathophysiology of the Transient Potential Receptor Vanilloid 6 (TRPV6) calcium channel.

Abstract

TRPV6 is a Transient Receptor Potential Vanilloid (TRPV) cation channel with high selectivity for Ca²⁺ ions. First identified in 1999 in a search for the gene which mediates intestinal Ca²⁺ absorption, its far more extensive repertoire as a guardian of intracellular Ca²⁺ has since become apparent. Studies on TRPV6-deficient mice demonstrated additional important roles in placental Ca²⁺ transport, fetal bone development and male fertility. The first reports of inherited deficiency in newborn babies appeared in 2018, revealing its physiological importance in humans. There is currently strong evidence that TRPV6 also contributes to the pathogenesis of some common cancers. The recently reported association of TRPV6 deficiency with non-alcoholic chronic pancreatitis suggests a role in normal pancreatic function. Over time and with greater awareness of TRPV6, other disease-associations are likely to emerge. Powerful analytical tools have provided invaluable insights into the structure and operation of TRPV6. Its roles in Ca²⁺ signaling and carcinogenesis, and the use of channel inhibitors in cancer treatment are being intensively investigated. This review first briefly describes the biochemistry and physiology of the channel, and analytical methods used to investigate these. The focus subsequently shifts to the clinical disorders associated with abnormal expression and the underlying pathophysiology. The aims of this review are to increase awareness of this channel, and to draw together findings from a wide range of sources which may help to formulate new ideas for further studies.