Although the exact mechanisms behind the cytosolic/nuclear shift of Sphk2 remain elusive, a study suggests a neuroprotective activity of cytosolic Sphk2 in Alzheimer’s disease, as there is an inverse correlation between its cytosolic expression and amyloid deposits in the frontal cortex and hippocampus of AD patients, coinciding with translocation to the nucleus [114]. Here, SPHK2 is linked to early-onset autosomal dominant Alzheimer disease.