Our study highlighted 4 potentially novel findings: (a) SEMA7A mutations were genetic risk factors for human NAFLD and its severity in humans (Tables 1 and 2); (b) the Sema7aR145W mutation significantly increased steatosis severity and NAS in mice (Figure 1); (c) the Sema7aR145W mutation markedly increased N-glycosylated Sema7a and its receptor integrin β1 proteins in hepatocyte surface membranes (Figure 6); and (d) the Sema7aR145W mutation caused intrahepatic lipid accumulation by enhancing PKC-α signaling–stimulated FA and TG synthesis and FA uptake (Figures 2–6). Here, PRKCA is linked to metabolic dysfunction-associated steatotic liver disease.