Itpr2, short for inositol 1,4,5-trisphosphate receptor, type 2, is an endoplasmic reticulum calcium-release channel. It plays a crucial role in calcium fluxes from the ER to the mitochondria, which are involved in multiple biological processes such as cellular senescence, myelination, and calcium homeostasis regulation. These processes are linked to various signaling pathways like the MAPK/ERK-CDK6/cyclin D1 axis [1,2].

Itpr2 knockout (KO) mice have been instrumental in understanding its functions. In Itpr2 KO mice, there is improved aging, with increased lifespan, better metabolic stress response, less immunosenescence, and reduced liver steatosis and fibrosis due to decreased cellular senescence. Ablation of ITPR2 also decreases the number of contacts between the mitochondria and the ER, and forced contacts can induce premature senescence [1]. In OL-specific Itpr2 KO adolescent mice, Ca2+ homeostasis is disturbed, myelination is inhibited, and anxiety/depressive-like behaviors are observed, accompanied by interrupted OPC proliferation [2]. Astrocytic calcium-deficient Itpr2-/-mice display abnormal resting-state functional connectivity in depression-related networks, especially in mPFC-related pathways [3].

In conclusion, Itpr2 is essential for maintaining normal physiological functions related to calcium-mediated processes. Studies using Itpr2 KO mouse models have provided insights into its role in aging, myelin-associated psychiatric disorders, and depression. These findings contribute to understanding the underlying mechanisms of these conditions and may offer potential therapeutic targets.