Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (By similarity). Receptor for the pro-inflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (PubMed:26099046). Activated by WNK3. Interacts with KLHL3 (By similarity). Interacts with IL18R1 in peritoneal macrophages; this interaction is increased by IL18 treatment (PubMed:26099046). Expressed predominantly in kidney, including in distal tubules (at protein level). Detected at low levels in heart, lung and liver. Not detected in normal aorta, but abundantly expressed in fatty streaks and advanced atherosclerotic lesions. In atherosclerotic lesions, expressed in macrophages, smooth muscle cells and endothelial cells (at protein level). In macrophages and T-lymphocytes, up-regulated by IL18. In endothelial cells and smooth muscle cells, up-regulated by IL1B, IL18 and TNF (at protein level). Ubiquitinated; ubiquitination is essential for regulation of endocytosis. Phosphorylated in response to IL18. Simultaneous knockout of APOE and SLC12A3 results lower plasma Mg(2+) compared to plasma levels in wild-type and APOE knockout animals. Simultaneous knockdown of APOE and SLC12A3 shows no significant differences in aortic root atherosclerotic lesion intima area and thoracic-abdominal aorta lipid deposition as compared to APOE and double APOE and IL18R1 knockout animals. In contrast, simultaneous knockdown of APOE, SLC12A3 and IL18R1 results in significantly smaller aortic root intimal size and decreased thoracic-abdominal aorta lipid deposition. The triple knockout mice exhibit lower plasma K(+) and Mg(2+) compared to plasma levels in wild-type animals. The effect on atherosclerosis is due to IL18 activation of bone marrow-derived leukocytes, and possibly vascular cells, rather than to kidney tubular disorders or electrolyte disturbances. Belongs to the SLC12A transporter family.