Other members of the Vps10p receptor family, SorLA and SorCS1-3, are not only shedded [7,31], but they are also gamma-secretase substrates [32], suggesting that both extracellular and intracellular released domains of the Vps10p receptor family may have functional activities in neurodegenerative diseases as described for SorLA in the pathology of Alzheimer’s disease [33]. The gene discussed is SORL1; the disease is early-onset autosomal dominant Alzheimer disease.