Mutations associated with atypical parkinsonism are found in VPS26A specifically (53, 74) and conversely VPS26B-Retromer is specifically enriched in the trans-entorhinal cortex region of the brain that is particularly vulnerable to Alzheimer’s disease-related neurodegeneration (75), emphasizing that spatially coordinated expression of subunit-specific endosomal sorting complexes and engagement of tissue-specific cargoes may be crucial to neuroprotection. Here, VPS26B is linked to early-onset autosomal dominant Alzheimer disease.