As further evidence for the key role of VPS10 domain proteins in AD, Andersen et al [81] and Lane et al [82] have recently demonstrated that SorLA modulation of APP metabolism requires binding of the SorLA cytoplasmic tail to VPS35 [81], and that another VPS10-domain protein, SorCS1, modulates coordinate risk of Alzheimer's disease and type 2 diabetes, apparently by controlling levels of both SorLA and VPS35 [82]. The gene discussed is SORL1; the disease is early-onset autosomal dominant Alzheimer disease.