Within early endosomes, p75NTR C-Terminal Fragment undergoes processing by gamma-secretase, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such a minimal complex is sufficient for secretase activity, although other components may exist. The p75NTR cleavage by gamma-secretase gives rise to a 20-kD ICD (IntraCellular Domain) fragment, and to a small peptide, the significance of which is unknown but that is analogous to the A-beta peptides generated from amyloid precursor protein. p75NTR ICD may have cytoplasmic and nuclear signalling functions and it is unstable.