Sphingolipids are both structural and bioactive compounds. In particular, ceramide and sphingosine 1-phosphate regulate cell fate, inflammation and excitability. 1-α,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) is known to play an important physiological role in growth and differentiation in a variety of cell types, including neural cells, through genomic actions mediated by its specific receptor, and non-genomic effects that result in the activation of specific signalling pathways. 1,25(OH) 2 D 3 and sphingolipids, in particular sphingosine 1-phosphate, share many common effectors, including calcium regulation, growth factors and inflammatory cytokines, but it is still not known whether they can act synergistically. Alterations in the signalling and concentrations of sphingolipids and 1,25(OH) 2 D 3 have been found in neurodegenerative diseases and fingolimod, a structural analogue of sphingosine, has been approved for the treatment of multiple sclerosis. This review, after a brief description of the role of sphingolipids and 1,25(OH) 2 D 3 , will focus on the potential crosstalk between sphingolipids and 1,25(OH) 2 D 3 in neural cells.Abbreviations 1,25(OH) 2 D 3 , 1-α,25-dihydroxyvitamin D3; AD, Alzheimer disease; APP, amyloid precursor protein; Aβ, amyloid β peptide;These Tables list key protein targets and ligands in this article which are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Southan et al., 2016), and are permanently archived in the Concise Guide to PHARMACOLOGY 2015/16 ( a,b,c,d,e,f Alexander et al., 2015a.