CLN5 and early-onset autosomal dominant Alzheimer disease: Previous studies showed that patient-derived CLN5 mutants, such as R121P, R121H, R145P, L358AfsX4, W379C, and Y392X, and the Alzheimer’s disease-linked loss-of-function CLN5 mutant N320S, are retained at the ER rather than trafficked to lysosomes (42, 44, 50, 51).