Atp2a2, also known as sarco/endoplasmic reticulum Ca2+ ATPase isoform 2 (SERCA2), encodes a Ca2+ pump on the endoplasmic reticulum (ER) membrane. It is crucial for intracellular Ca2+ signaling, which is involved in various biological processes such as cell adhesion, metabolism, and neurotransmission [1,2,3].

In a study of Atp2a2 heterozygous brain-specific conditional knockout (hetero cKO) mice, the ER membranes from the hetero cKO mouse brain had decreased Ca2+ uptake activity. Atp2a2 heterozygous neurons showed slower decays of cytosolic Ca2+ levels after depolarization. The hetero cKO mice exhibited altered behavioral responses and fear memory impairments, along with higher extracellular dopamine levels in the NAc, suggesting that haploinsufficiency of Atp2a2 in the brain causes prolonged cytosolic Ca2+ transients and enhanced dopamine signaling, a common feature in mood disorders and schizophrenia [1]. Also, in a Shih Tzu with Darier disease, a heterozygous missense variant in Atp2a2 was identified, highlighting its role in this skin disorder [2].

In conclusion, Atp2a2 is essential for intracellular Ca2+ regulation, which impacts multiple biological processes. The study of Atp2a2 using gene knockout models, such as the brain-specific conditional knockout mouse model, has revealed its role in mental disorders like mood disorders and schizophrenia, as well as in skin diseases like Darier disease. Understanding Atp2a2 provides insights into the underlying mechanisms of these diseases and may offer potential therapeutic targets.