Akt2, also known as Protein kinase B-β (Pkb-β), is a serine/threonine protein kinase that is a crucial component of the Phosphatidylinositol 3 kinase/Akt/Mammalian target of rapamycin (PI3K/mTOR) signaling axis [2,4]. It plays a vital role in controlling cell growth, proliferation, survival, and is also involved in processes like angiogenesis, cell migration, invasion, and metastasis [2]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In a study on non-neovascular AMD, Akt2 overexpression in the RPE of aging Akt2 KI mice led to a dry AMD-like phenotype and decline in retinal function. Inhibition of the AKT2/SIRT5/TFEB pathway in the RPE induced lysosome/autophagy signaling abnormalities, disrupted mitochondrial function, and contributed to drusen formation [1]. In hepatosteatosis and liver cancer, hepatic AKT2 hyperactivation through a gain-of-function mutation (Akt2E17K) in mice caused spontaneous hepatosteatosis, injury, inflammation, fibrosis, and eventually HCC [3]. For nicotine response, Akt2 cKO mice showed increased astrocyte morphological complexity during nicotine exposure and reduced nicotine preference, indicating the importance of Akt2 in astrocytic nicotine responses [5].

In conclusion, Akt2 is essential in multiple biological processes and is involved in diseases such as non-neovascular AMD, hepatosteatosis-associated HCC, and potentially in nicotine-related behaviors. Studies using KO and CKO mouse models have been crucial in uncovering these roles, providing insights into the mechanisms underlying these disease conditions and potentially guiding the development of targeted therapies.