Atp2a2, also known as SERCA2, encodes a Ca2+ pump on the endoplasmic reticulum (ER) membrane. It is crucial for intracellular Ca2+ signaling, which is involved in multiple biological processes [1,2,3,4].

In Atp2a2 heterozygous brain-specific conditional knockout (hetero cKO) mice, the ER membranes from the brain showed decreased Ca2+ uptake activity. The hetero cKO mice had slower decays of cytosolic Ca2+ levels in neurons after depolarization, leading to altered behavioral responses and fear memory impairments, along with enhanced dopamine signaling and higher extracellular dopamine levels in the NAc. This indicates that haploinsufficiency of Atp2a2 in the brain causes prolonged cytosolic Ca2+ transients and potentially enhanced dopamine signaling, a feature associated with mood disorders and schizophrenia [1].

In conclusion, Atp2a2 is essential for maintaining proper intracellular Ca2+ homeostasis through its role as an ER Ca2+ pump. The study of Atp2a2 using gene knockout models, such as the brain-specific hetero cKO mice, has revealed its significance in neuropsychiatric disorders, highlighting the potential link between its mutations and the development of these conditions.