Research advances in structure and functions of complement C1q/tumor necrosis factor-related protein 4: A review

Complement C1q/tumor necrosis factor-related protein 4 (CTRP4) is a unique member of the CTRP family, distinguished by its two tandem C1q globular domains and broad tissue distribution, with particularly high expression in the central nervous system and adipose tissue. Initially recognized for its role in metabolic regulation, CTRP4 has since emerged as a pleiotropic adipokine involved in the pathogenesis of various disorders, including type 2 diabetes mellitus, non-alcoholic fatty liver disease, inflammatory diseases, cardiovascular conditions, and multiple types of cancer. Mechanistically, CTRP4 mediates its diverse functions through binding to the nucleolin receptor and modulation of key signaling pathways such as NF-κB, STAT3, AMPK, and PI3K/Akt. Recent studies have also implicated CTRP4 in neurocognitive processes, mood regulation, and bone metabolism, further broadening its biological significance. Despite these advances, critical gaps remain in our understanding of the upstream regulatory mechanisms governing CTRP4 expression, its tissue-specific actions, and its translational potential in clinical applications. This review provides a comprehensive overview of the molecular structure, expression patterns, and multifunctional roles of CTRP4, proposing it as a promising target for biomarker development and therapeutic intervention across multiple disease.