In keeping with these findings, tissue expression of PNPLA3 is significantly enhanced in biopsies of patients carrying the p.I148M polymorphism, whereas the rare rs2294918 PNPLA3 (p.E434K) variant attenuates the impact of the p.I148M on steatosis and circulating liver enzymes in NAFLD patients, whereby down-modulating PNPLA3 expression on the LDs (up to 50%) [57,60]. Here, PNPLA3 is linked to steatosis.