Ursolic acid alleviates MASLD in HFD-induced models by inhibiting Th17 differentiation through the SPP1-ITGB1/CD44-ERK pathway, thereby reducing TG, TC, ALT, AST, IL-17A, TNF-α, and IL-6, and diminishing hepatic lipid deposition. Here, CD44 is linked to metabolic dysfunction-associated steatotic liver disease.