Loss of intracellular calcium homeostasis may contribute to the opacification of lens tissue during cortical cataract formation. In healthy lenses, the concentration of intracellular calcium is maintained at levels far below electrochemical equilibrium but the identity of the calcium extrusion mechanism in lens fiber cells has remained elusive. Previous studies focused on the role of plasma membrane calcium ATPases and sodium-calcium exchangers. Here, we examined the expression of mRNA transcripts encoding potassium-dependent sodium-calcium exchangers (Nckx's, encoded by the Slc24 gene family) in the mouse lens. The most abundant of the five Slc24 family members was Slc24a4 (Nckx4). Notably, Slc24a4 was the only family member with increased expression in fiber cells. Using an antibody raised against recombinant mouse Nckx4, we showed that the protein is expressed strongly in the outer cortical fibers, consistent with results of in situ hybridization experiments and earlier mass spectrometry analysis. To test the role of Nckx4 directly, we generated mice in which Slc24a4 was deleted conditionally in lens tissue. In conditional knockout animals, the level of Nckx4 protein was reduced to background levels without a discernible effect on lens growth or transparency. Thus, despite its relative abundance in the lens, Nckx4 does not appear to have an indispensable role in the maintenance of lens clarity.