Cation Chloride Cotransporter Interacting Protein 1 (CIP1)

The relative expression level of the neuron-specific SLC12A5 and the Na+-K+-2Cl- cotransporter SLC12A2 appears to determine whether neurons respond to GABA with a depolarizing, excitatory response or with a hyperpolarizing, inhibitory response. The four K+-Cl- cotransporter genes are co-expressed to varying degrees in most tissues, with further roles in cell volume regulation, transepithelial salt transport, hearing, and function of the peripheral nervous system. The transported substrates of the remaining two SLC12 family members, SLC12A8 and SLC12A9, are as yet unknown. Inactivating mutations in three members of the SLC12 gene family result in Mendelian disease; Bartter syndrome type I in the case of SLC12A1, Gitelman syndrome for SLC12A3, and peripheral neuropathy in the case of SLC12A6.