The sodium–calcium exchanger (NCX) of plasma membrane is expressed in any animal cell. The specific role of its three isoforms (NCX1–3) is not yet established. Their levels vary considerably during murine postnatal development. In particular, in skeletal muscle, NCX1 expression decreases gradually upon aging while reciprocal changes take place for NCX3. NCX2 expression is restricted to brain and smooth muscles. The data on SDS-gel mobility shifts indicate that all three isoforms undergo Ca2+-dependent conformational changes, and that an exchanger regulatory Ca2+-binding domain interacts directly with mutually exclusive exons A and B inducing two different NCX1 conformations.