Our findings confirm that SLC9A6‐126aa, a novel upstream regulator of the MAPK cascade, promotes lipid dyshomeostasis in NAFLD via CD36‐mediated phosphorylation of p38 and ERK, supporting the above notion of p38‐ and ERK‐MAPK pathways‐mediated reprogramming of lipid metabolism. Here, SLC9A6 is linked to metabolic dysfunction-associated steatotic liver disease.