Atp2a2, also known as SERCA2, encodes a Ca2+ pump on the endoplasmic reticulum (ER) membrane. This pump is crucial for intracellular Ca2+ signaling, which is involved in numerous biological processes such as cell adhesion, differentiation, and apoptosis. The regulation of Ca2+ levels by Atp2a2 is also associated with multiple pathways related to normal cellular function and disease development [1,2,3].

In Atp2a2 heterozygous brain-specific conditional knockout (hetero cKO) mice, the ER membranes from the brain showed decreased Ca2+ uptake activity. The cytosolic Ca2+ level decays were slower in Atp2a2 heterozygous neurons after depolarization. These mice exhibited altered behavioral responses and fear memory impairments, along with enhanced dopamine signaling, suggesting that haploinsufficiency of Atp2a2 in the brain leads to prolonged cytosolic Ca2+ transients and potentially enhanced dopamine signaling, a common feature in mood disorders and schizophrenia [1]. Additionally, in a Shih Tzu with Darier disease, a heterozygous missense variant in the ATP2A2 gene was identified, highlighting its role in this skin disorder [2].

In conclusion, Atp2a2 is essential for maintaining proper intracellular Ca2+ signaling. Research using gene knockout models, such as the Atp2a2 hetero cKO mouse, has revealed its significance in neurological and dermatological diseases. These findings enhance our understanding of the biological functions of Atp2a2 and its role in disease mechanisms, potentially paving the way for new therapeutic strategies.