PNPLA3 and fatty liver disease: To date, the majority of research interest in PNPLA3 has centered on understanding the mechanisms that link the rs738409[G] (encoding I148M) polymorphism and NAFLD progression and has resulted in an appreciation that loss of PNPLA3-mediated TG hydrolase activity alone is unlikely to cause hepatic steatosis, as ablation of wild-type PNPLA3 does not alter TG levels (77).