Alkaline ceramidase (ACER)

Alkaline ceramidases (ACERs) are a family of three transmembrane enzymes (ACER1, ACER2, and ACER3) that catalyze the hydrolysis of ceramides into sphingosine and free fatty acids at an alkaline pH. These enzymes play a critical role in regulating the balance of bioactive sphingolipids, specifically by controlling the levels of ceramide, which promotes apoptosis and cell cycle arrest, and its metabolite sphingosine-1-phosphate (S1P), which promotes cell survival and proliferation. ACER1 is primarily expressed in the skin and is essential for keratinocyte differentiation and skin barrier function. ACER2 is localized to the Golgi apparatus and is often upregulated in response to DNA damage or stress, mediating programmed cell death. ACER3 is more ubiquitously expressed and shows a preference for long-chain ceramides; its dysfunction is linked to progressive leukodystrophy and other neurodegenerative conditions. In oncology, ACERs are viewed as potential therapeutic targets because their inhibition can lead to the accumulation of ceramides, thereby inducing tumor cell death and sensitizing cells to chemotherapy.

Other names

ALCERAlkaline CDaseCeramidase alkalineACER1ACER2ACER3

Inhibition of ceramide hydrolysis to increase pro-apoptotic ceramide levels and decrease pro-survival sphingosine-1-phosphate (S1P) levels.