Interestingly, Alzheimer's disease is associated with SphK2, a key player of the UFIT pathway, that unlike SphK1, is upregulated in brain samples from patients with Alzheimer's disease, and as a result leads to S1P overproduction in neurons (Takasugi et al., 2011). Here, SPHK1 is linked to early-onset autosomal dominant Alzheimer disease.