Alox15, also known as 15-lipoxygenase-1 or 12/15-lipoxygenase (12/15-LOX), is an enzyme that oxidizes polyunsaturated fatty acids, generating bioactive lipid metabolites. It is involved in oxidative and inflammatory responses, and its metabolites play roles in gene expression and cytokine production related to inflammation and its resolution [2].

Myocardial-specific knockout of Alox15 in mice alleviated myocardial ischemia-reperfusion (I/R) injury, restored cardiac function, and reduced cardiomyocyte ferroptosis. 15-Hydroperoxyeicosatetraenoic acid (15-HpETE), an Alox15-derived metabolite, was identified as a trigger for cardiomyocyte ferroptosis [1].

Intestinally-targeted transgenic expression of ALOX15 in mice inhibited dextran sodium sulfate-induced colitis from promoting azoxymethane-induced colorectal tumorigenesis, demonstrating its role in suppressing inflammation-driven colorectal tumorigenesis [3].

In asthma, silencing ALOX15 in HDM/LPS-stimulated 16HBE cells decreased ferroptosis, indicating its role in asthma-related ferroptosis [4].

Macrophage-derived exosomes with miRNA-660-5p attenuated ALOX15 expression in cervical cancer cells to suppress ferroptosis, and ALOX15 expression was positively associated with good prognosis in cervical cancer [5].

Electroacupuncture relieved neuropathic pain by suppressing ferroptosis in the dorsal root ganglion via the SAT1/ALOX15 signaling pathway [6].

DHODH inhibited ALOX15 expression by inhibiting P53, reducing neuronal ferroptosis after spinal cord injury [7].

In conclusion, Alox15 is crucial in processes like inflammation, ferroptosis, and disease development. Gene-knockout mouse models have significantly contributed to understanding its role in diseases such as myocardial I/R injury, colorectal cancer, asthma, cervical cancer, neuropathic pain, and spinal cord injury. These studies offer potential therapeutic targets for treating these conditions.