In this study, we demonstrate that a heterozygous AD mutation in LZTR1 caused NS-like phenotypes, including cardiac hypertrophy, low birth weight, short birth stature, and a distinctive facial appearance using AD mutation knock-in mouse models, such as Lztr1R409C/+ and Lztr1G245R/+ mice. Here, LZTR1 is linked to Alzheimer disease.