The anti-diabetic drugs metformin, phenformin and thiazolidenediones exploited in NAFLD/NASH therapy are all AMPK-activators, as are many natural products i.e. salicylates, resveratrol, epigallocatechin, capsaicin, curcumin and garlic, fueling the current pharmaceutical quest for novel, even more selective AMPK-activators35, 69. Here, PRKAA1 is linked to metabolic dysfunction-associated steatohepatitis.