[10] Based on evidence that a gamma-secretase inhibitor binds to the fragments,[11] the cleaved presenilin complex is considered to be the active form.

Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma secretase activity or themselves are protease enzymes.

Multiple alternatively spliced transcript variants have been identified for this gene, the full-length natures of only some have been determined.

In the prenilin 1 null mutant drosophila, Notch signaling is abolished and it displays a notch-like lethal phenotype.

[20] Considered as a negative regulator in wnt signaling pathway, presenilin-1 was also found to play a role in beta-catenin phosphorylation.

[21] The study also further illustrates that the deficiency of presenilin 1 disconnects the sequential phosphorylation and thus disrupts the normal wnt signaling pathway.

[21] Transgenic mice that over-expressed mutant presenilin-1 show an increase of beta-amyloid-42(43) in the brain, which suggest presenilin-1 plays an important role in beta-amyloid regulation and can be highly related to Alzheimer's disease.

[22] Further study conducted in neuronal cultures derived from presenilin-1 deficient mouse embryos showed that cleavage by alpha- and beta- secretase was still normal without the presence of presenilin-1.