Metabolic Messengers: endotrophin

Endotrophin (ETP), a C-terminal cleavage fragment of the collagen VI α3 chain, has emerged as a key mediator of fibroinflammation and a clinically relevant biomarker of disease progression. Accumulating evidence from both preclinical models and human studies implicates elevated ETP levels as a driver of tissue remodelling, metabolic dysfunction, inflammation and fibrosis across multiple organ systems. Increased ETP has been linked to obesity-associated adipose tissue dysfunction, steatotic liver disease, breast cancer progression, chronic kidney disease and cardiovascular disease, underscoring its broad pathological relevance. The convergence of mechanistic and clinical data positions ETP as a promising therapeutic target across a range of diseases linked by common ETP-driven dysfunction. Here we synthesize current knowledge of ETP's regulation and functions, critically evaluate its role in diverse disease contexts and outline key unanswered questions and emerging strategies for therapeutic intervention.