Table 1.

Potential therapeutic use of the retromer chaperones in human disease. List of neurological and non-neurological diseases with established links to the retromer pathway

	Pathogenic link‡	Established pathway§	Animal models
Alzheimer’s disease*	+ + +	APP endosomal trafficking	+ + +
Parkinson’s disease*	+ + +	Vps35 mutations, impaired autophagy	+
Down’s syndrome*	+	SNX27 dysfunction	+ +
HSP*	+	Retromer/WASH complex interaction	+
Cerebral lipofuscinosis*	+	Deficient retromer recruitment machinery	+
Nieman Pick type C1*	+/–	ESCRT-mediated endosomal cholesterol trafficking	+
Type II diabetes†	+ +	SORCS1 (Vps10 family) dysfunction	+ +
Osteoporosis†	+	Vps35 deficiency, deregulation of RANK signaling	+

HSP = hereditary spastic paraplegia; APP = amyloid precursor protein; Vps = vacuolar protein sorting; WASH = Wiskott–Aldrich Syndrome Protein and SCAR Homolog; ESCRT = Endosomal Sorting Complex Required for Transport; SORCS1 = sortilin-related VPS10 domain containing receptor; RANK = Receptor activator of nuclear factor-kappa B

*Neurological disease

^†Non-neurological disease

^‡The number of plus symbols depicts the amount/strength of experimental evidence associated in each disease with the role of the retromer complex/pathway

^§A short description of the molecular/cellular pathway affected in each disease is shown. For further details please refer to the cited bibliography in the main text