PNPLA3 and fatty liver disease: In contrast, a missense genetic variant in PNPLA3 (I148M) in humans is strongly associated with fatty liver disease (Romeo et al., 2008) by reduced hydrolase activity (Huang et al., 2011) and disruption of Pnpla2/ATGL function on the lipid droplet surface (BasuRay et al., 2019; Wang et al., 2019).