Adult neurons in the mammalian central nervous system (CNS) fail to regenerate after injury due to a number of factors including the reduced intrinsic growth capacity together with the hostile environment of the injured CNS microenvironment [1-4]. However recent studies have shown that modifying the intrinsic growth capacity through a number of cell signalling pathways can promote regeneration of adult CNS neurons. For example, intrinsic factors such as cyclic adenosine monophosphate (cAMP), mammalian target of rapamycin (mTOR), and the repressors phosphatase and tensin homolog (PTEN) and suppressor of cytokine signalling 3 (SOCS3) promote CNS axon regeneration [5-7]. 

Metabolic dysfunction-associated steatotic liver disease (MASLD) is comprised of a spectrum of conditions, which is a progressive form of liver disease ranging from simple steatosis to steatohepatitis. The liver regulates fat metabolic homeostasis through de novo lipogenesis, fatty acid uptake and oxidation, low-density lipoprotein secretion in hepatocytes.

The liver emerges as an ultimate metabolic nexus—a polyfunctional organ that simultaneously performs biochemical detoxification, macromolecular processing, and systemic nutrient governance. While hepatic stellate cells (HSCs) were historically confined to their fibrogenic identity, their broader homeostatic orchestration remained enigmatic. RSPO3 as a linchpin in hepatocyte dynamics, with targeted pharmacological modulation enhancing hepatic lobular repatterning, regenerative capacity, and metabolic optimization.