STX5 defects have also been shown to affect processing of AD-related proteins. In AD, amyloid precursor protein (APP) undergoes a series of proteolytic events by β- and γ-secretases to create the amyloidogenic variants of β-amyloid (Aβ) that are longer and more likely to form aggregates (Peric and Annaert, 2015). Presenilins form a complex with γ-secretase, and mutations in presenilin 1 (PS1) are the most frequently associated mutations found in AD which result in increased production of Aβ, or altered ratios of amyloid peptide species (Hardy, 2006; Saito et al., 2011; De Strooper et al., 2012). Overexpressed STX5 was shown to co-localize with and directly bind to PS1. Further, STX5 overexpression increased the accumulation of APP in the ER and cis-Golgi and inhibited Aβ secretion in a neuroblastoma cell line (NG108-15)(Suga et al., 2005b). In NG108-15 cells expressing the familial AD mutation PS1ΔE9, STX5 was shown to have a decreased association with presenilin. A study of ER stress in an AD model demonstrated that ER stressors can increase synthesis of STX5 and its accumulation in the ER-Golgi intermediate compartment (ERGIC) and transport vesicles. Thus, upregulation of trafficking machinery induced by ER stress could be a cellular mechanism for correcting the accumulation of the amyloidogenic cleavage products of APP (Suga et al., 2015).