Potassium-dependent sodium-calcium exchanger (NCKX) isoforms and neuronal function

[Display omitted] •K+-dependent Na+/Ca2+-exchangers (NCKX), encoded by a five-member gene family, are essential for neuronal Ca2+ transport.•NCKX genes are associated with human diseases that impact vision, tooth enamel, and skin pigment development.•NCKX1, NCKX2 and NCKX4 are important for visual adaptation in retinal rods and cones.•NCKX2 is important for synaptic plasticity underlying experience-dependent learning and spatial working memory.•NCKX4 is critical for olfactory signal transduction, for satiety signaling in the brain, and for dental enamel production. K+-dependent Na+/Ca2+-exchangers (NCKX) are a relatively recently described five-member gene family of transporters which play a quantitatively significant role in neuronal Ca2+ transport. In this review we highlight the important individual contributions these transporters make to cellular Ca2+ homeostasis and neuronal function. Notably, different members of the family make distinct, non-redundant, contributions to critical behavioural pathways. In particular, NCKX proteins regulate the kinetics, termination and adaptation of Ca2+ signals in sensory transduction neurons in the olfactory and visual systems. Similar contributions to shaping the spatial and temporal features of Ca2+ signals in neurons at other key brain locations have important consequences for the circuitry influencing control of satiety, for experience-dependent motor learning and spatial working memory retention, as well as in the protection of neurons in the face of toxic stimuli. NCKX proteins are also key contributors to a variety of events in other tissues. The connection between NCKX isoform function and human phenotype and disease is an emerging area, and we anticipate that future research will reveal rich new details in the coming years.