title: Mg2+ homeostasis: the balancing act of TRPM6.
abstract: OBJECTIVE
  The tight control of blood magnesium (Mg) levels is of central importance for numerous physiological processes. A persistent low Mg status (hypomagnesemia) is associated with severe health risks and is involved in the pathogenesis of type 2 diabetes mellitus, osteoporosis, asthma, and heart and vascular diseases. The current view has expanded significantly as a result of the identification of novel genes and regulatory pathways involved in hypomagnesemic disorders. This review aims to give an up-to-date overview of transient receptor potential melastatin 6 (TRPM6) regulation and its role in the maintenance of Mg homeostasis.
  
  
  RESULTS
  The epithelial Mg channel TRPM6 is considered to be the Mg entry pathway in the distal convoluted tubule of the kidney, where it functions as gatekeeper for controlling the body's Mg balance. Various factors and hormones contribute not only to the function, but also to the dysregulation of TRPM6, which has a substantial impact on renal Mg handling. Recent genetic and molecular studies have further elucidated the signaling processes of epithelial Mg transport, including their effect on the expression and function of TRPM6.
  
  
  CONCLUSIONS
  Knowledge of TRPM6 functioning is of vital importance to decipher its role in Mg handling and will, in particular, provide a molecular basis for achieving a better understanding of Mg mal(re)absorption and hence systemic Mg balance.
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jenny
authors.initials: J
authors.lastname: van der Wijst
authors.forename: René J M
authors.initials: RJ
authors.lastname: Bindels
authors.forename: Joost G J
authors.initials: JG
authors.lastname: Hoenderop
mesh_terms: D004848:Epithelium / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D008274:Magnesium / Q000097:blood / Q000378:metabolism*; D009397:Nephrocalcinosis / Q000235:genetics / Q000378:metabolism; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D050053:TRPM Cation Channels / Q000235:genetics* / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; D008274:Magnesium