Akr1b8, the murine ortholog of human AKR1B10 [5], is an enzyme that may be involved in fatty acid synthesis as it associates with murine acetyl-CoA carboxylase-α in colon cancer cells [5]. It is secreted via a lysosomes-mediated non-classical pathway [4].

Akr1b8 deficiency in mice leads to multiple pathological conditions. In the intestine, it impairs the intestinal epithelial cell (IEC) barrier function, increasing colonic epithelial permeability, reducing Muc2 expression, and leading to infiltration of neutrophils and mast cells [3]. AKR1B8-deficient mice develop severe acute colitis at a low dose of dextran sulfate sodium (DSS), with increased bacterial invasion and activation of innate immunity, specifically the TLR4 signaling pathway [1]. In diet-induced non-alcoholic steatohepatitis (NASH) in mice, genetic silencing of Akr1b8 reduces the expression of pro-inflammatory cytokines from hepatocytes [2]. Also, in the context of facial nerve injury repair in rats, knocking down Akr1b8 in Schwann cells decreases the expression of monocyte chemoattractant protein-1 and interleukin-6, suggesting its role in regulating the interaction between Schwann cells and macrophages to promote nerve regeneration [6].

In conclusion, Akr1b8 is crucial for maintaining normal physiological functions in the intestine, liver, and during nerve repair processes. Studies using Akr1b8-deficient mouse models have revealed its significance in diseases such as colitis and NASH, highlighting its potential as a therapeutic target for these conditions.