Akr1a1, also known as aldehyde reductase, is a member of the aldo-keto reductase superfamily. It catalyzes the reduction of aldehyde groups to their corresponding alcohols in an NADPH-dependent manner [4]. It is involved in multiple biological processes, such as the transformation of D-glucuronate to L-gulonate in the synthesis of L-ascorbic acid (vitamin C) [2], and is also implicated in the detoxification of toxic aldehydes [3]. It may play a role in metabolic pathways related to drug conjugation and excretion [1]. Genetic models, like knockout mice, are valuable for studying its functions.

In AKR1A1 knockout mice with vitamin C deficiency, there is aberrant bone formation and osteoporosis, and kefir peptides can ameliorate this condition by promoting osteoblastogenesis and inhibiting osteoclastogenesis [2]. In alcohol-associated liver disease, Akr1a1 knockout mice fed with alcohol show a lower survival rate and more severe liver injury, with increased pro-inflammatory cytokines, oxidative stress, lipid accumulation, and fibrosis, suggesting that AKR1A1 plays a liver-protective role by reducing 4-HNE accumulation and p53 activation [4]. In the context of kidney injury, deletion of Akr1a1 in mice increases protein S-nitrosylation, protects against acute kidney injury, and improves survival, revealing its role in transducing eNOS activity to reprogram intermediary metabolism [5].

In conclusion, Akr1a1 is crucial in various biological processes including vitamin C synthesis, bone metabolism, liver protection, and kidney injury response. Studies using AKR1A1 knockout mouse models have significantly advanced our understanding of its functions in osteoporosis, alcohol-associated liver disease, and kidney injury, highlighting its potential as a therapeutic target in these disease areas.