Although different KLK8 substrates, e.g., ephrin receptor B2 (EPHB2) [46], fibronectin [47], neuregulin-1 [48], and the neural cell adhesion molecule L1 (L1CAM) [49], have been long known to be directly involved in the pathophysiology of AD, it was not until recently that the role of KLK8 in the context of AD was recognized. This evidence concerns the gene L1CAM and Alzheimer disease.