Lars2, an enzyme responsible for synthesizing mitochondrial leucyl-tRNA, is crucial for maintaining mitochondrial function. It is involved in pathways such as the phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT) pathway. Its proper function is of great biological importance as it impacts various cellular processes related to mitochondrial activity [1,3].

In Alzheimer's disease (AD) research, knockdown of Lars2 in mouse neuroblastoma cells (neuro-2a cells) and primary cortical neurons led to morphological changes and decreased density in mouse hippocampal neurons. In vivo, knockout of lars2 in hippocampal neurons caused cognitive impairment as shown by the Barnes maze test, the novel object recognition test, and nest-building experiments. Downregulated Lars2 expression impeded the PI3K-AKT pathway, activating GSK3β, which led to excessive phosphorylation of Tau protein and subsequent neuronal degeneration, suggesting Lars2 as a potential therapeutic target for AD [1].

In ovarian granulosa cells, silencing of Lars2 inhibited cell proliferation and promoted apoptosis, induced mitochondrial dysfunction and ROS accumulation, indicating its role in the etiology of premature ovarian insufficiency (POI) [2].

In conclusion, Lars2 is essential for mitochondrial function and is involved in multiple disease-related biological processes. Gene knockout models in mice have been instrumental in revealing its role in AD and POI, providing valuable insights into the underlying mechanisms of these diseases and potential therapeutic strategies related to Lars2.