Regulator of calcineurin 2 (RCAN2), also known as ZAKI4 and DSCR1L1, is expressed as two isoforms differing at their N-terminus. The longer of the two (isoform 1) is expressed exclusively in the brain, while isoform 2 is ubiquitously expressed, with highest expression in brain, heart, and muscle. Both isoforms bind to the catalytic subunit of calcineurin, a Ca++-dependent protein phosphatase involved in several neuronal functions, though their C-terminal region and inhibit calcineurin's activity. Unlike isoform 1 of RCAN2, the expression of the second isoform is not induced by the thyroid hormone T3. RCAN2 is a member of a family of three endogenous calcineurin regulators that are located near the minimal supernumerary fragment of chromosome 21 in individuals with Down syndrome, suggesting that they play a role in this syndrome.