Endotrophin as a biomarker and mediator in cardiovascular-kidney-metabolic syndrome: current insights and remaining questions

Endotrophin, a biologically active fragment derived from the α3 chain of collagen type VI, has emerged as both a risk biomarker and a potential pathogenic factor in cardiovascular-kidney-metabolic (CKM) syndrome. Over the past decade, research has shed light on its role in various noncommunicable diseases, emphasizing its signaling properties and diagnostic potential. Despite these advances, significant gaps remain in our understanding of how endotrophin contributes to CKM pathophysiology and whether targeting it therapeutically could modify disease progression. This narrative review synthesizes current evidence on endotrophin biological functions and clinical associations, drawing from both experimental and clinical studies. In addition, it identifies critical areas where further investigation is required, including the molecular mechanisms linking endotrophin to CKM-related tissue dysfunction and its causal role in disease development. By mapping current knowledge and highlighting research priorities, this review aims to advance the field toward a more complete understanding of endotrophin as a potential therapeutic target.