Accumulating evidence suggests that an imbalance of sphingolipids may play a role in neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS).[43] In the current study, we demonstrate that SPHK2 not only works as a cofactor of AHR/ARNT for downstream target gene activation, but also enhances AHR‐mediated target gene expression. The gene discussed is ARNT; the disease is amyotrophic lateral sclerosis.