NCC knockout mice demonstrated changes similar to those observed in Gitelman’s syndrome, in which NCC is dysfunctional (below), including hypomagnesemia, hypocalciuria, and increased renin expression (determined in the kidney; Schultheis et al., 1998; Loffing et al., 2004; Alshahrani et al., 2017a). Here, REN is linked to familial primary hypomagnesemia.