Acer3, also known as alkaline ceramidase 3, is an enzyme that catalyzes the hydrolysis of ceramide, dihydroceramide, and phytoceramide into sphingosine (SPH), dihydrosphingosine (DHS), and phytosphingosine (PHS), respectively, along with a free fatty acid. It is a member of the alkaline ceramidase (ACER) family, which plays a crucial role in regulating sphingolipid metabolism and various biological processes [3].

In acute myeloid leukemia (AML), in silico analysis showed that ACER3 expression inversely correlates with overall survival of patients. Inhibition of Acer3 expression in human AML cells using an shRNA-encoding lentivirus system led to decreased cell growth, colony formation, elevated apoptosis, and lower AKT signaling, suggesting that ACER3 contributes to AML pathogenesis [1]. In cholestatic liver injury (CLI), ACER3 expression is upregulated in the cholestatic liver and positively correlated with the severity of CLI in patients. Acer3 ablation in female mice increased ceramide(d18:1/18:1) and attenuated bile duct ligation-induced CLI with reduced hepatic necrosis, inflammation, and fibrosis [2].

In conclusion, Acer3 is essential in regulating sphingolipid metabolism. Studies using gene-knockdown or knockout models in AML and CLI have revealed its contribution to these disease conditions. Understanding Acer3's function provides insights into the underlying mechanisms of these diseases, potentially leading to new therapeutic strategies.

References:

1. Chen, Chen, Yin, Yancun, Li, Chunling, Wang, Yuesi, Zhang, Cheng Cheng. 2016. ACER3 supports development of acute myeloid leukemia. In Biochemical and biophysical research communications, 478, 33-38. doi:10.1016/j.bbrc.2016.07.099. https://pubmed.ncbi.nlm.nih.gov/27470583/

2. Liao, Leyi, Liu, Ziying, Liu, Lei, Li, Chuanjiang, Wang, Kai. 2025. Targeting the ceramidase ACER3 attenuates cholestasis in mice by mitigating bile acid overload via unsaturated ceramide-mediated LXRβ signaling transduction. In Nature communications, 16, 2112. doi:10.1038/s41467-025-57330-7. https://pubmed.ncbi.nlm.nih.gov/40025008/

3. Xu, Ruijuan, Antwi Boasiako, Paul, Mao, Cungui. 2020. Alkaline ceramidase family: The first two decades. In Cellular signalling, 78, 109860. doi:10.1016/j.cellsig.2020.109860. https://pubmed.ncbi.nlm.nih.gov/33271224/