Interestingly, the enzymatic reaction products, SPC and GSP, which are essential surrogates to determine whether SM GCer deacylase is functioning in situ in the epidermis, is significantly increased in the nonlesional and lesional SC of patients with AD compared with HCs, and is reciprocally related to the decreased levels of ceramides in a similar group of patients with AD. Here, GNAS is linked to Alzheimer disease.