The decrease in glycosylation processes associated with the hyperactivation of calpain-2, and the overexpression of Reg-1α observed in Alzheimer disease, prompt us to further investigate the calpain-2/Reg-1α crosstalk as well as the role of this new cleavage and its regulation by glycosylation in the context of neurodegenerative diseases. The gene discussed is REG1A; the disease is early-onset autosomal dominant Alzheimer disease.