Vital but vulnerable: Human TRPV6 is a trade-off of powerful Ca2+ uptake and susceptibility to epithelial barrier dysfunction

Robust Ca2+ absorption is controlled by the highly Ca2+-permeable channels TRPV5 and TRPV6 in the kidney and intestine of terrestrial vertebrates, to fulfill the body's demand for Ca2+. Recently, a pathogenic role of TRPV6 was revealed in alcohol-associated endotoxemia; the intestinal barrier function is compromised by oxidative stress via TRPV6-mediated Ca2+ dysregulation. TRPV6-mediated Ca2+ absorption vital to maintain homeostasis is vulnerable to alcohol-induced malactivation.