Slc12a2, encoding the Na-K-2Cl cotransporter-1 (NKCC1), is a member of the SLC12 gene family which encodes electroneutral cation-coupled chloride co-transporters. It plays crucial roles in multiple biological processes, including corticogenesis, inner ear endolymph homeostasis, and is involved in ion transportation pathways [1,4]. Genetic models, such as knockout mouse models, have been valuable in studying its functions.

Male and female mice lacking Slc12a2 specifically in insulin-secreting β-cells (Slc12a2βKO) develop a metabolic syndrome-like phenotype, including overweight, glucose intolerance, insulin resistance, and metabolic abnormalities. These mice have reduced β-cell mass and mild secretory dysfunction. The reduced satiation control of feeding in these mice precedes the onset of overweight [2]. Also, mice lacking Slc12a2 in pancreatic β-cells (Nkcc1βKO) show reduced in vitro insulin responses to glucose, islet hypoplasia, and excessive weight gain with progressive metabolic syndrome when fed a standard chow diet [3].

In conclusion, Slc12a2 is essential for normal physiological functions. Its loss in specific cell types, as demonstrated in KO mouse models, reveals its key role in metabolic regulation, especially in relation to β-cell function and the development of metabolic syndrome. Additionally, Slc12a2 is associated with neurodevelopmental disorders and cochleovestibular defects [1].