CILP2: From ECM Component to a Pleiotropic Modulator in Metabolic Dysfunction, Cancer, and Beyond

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Cartilage intermediate layer protein 2 (CILP2) was initially identified as an extracellular matrix component but is now recognized as a pleiotropic secretory protein.
• Emerging evidence highlights CILP2's significant roles in various physiological and pathological processes, including metabolic disorders and cancer.

Purpose of the Study:

• To review and synthesize current evidence on CILP2's multifaceted roles in human diseases.
• To establish CILP2 as a key modulator in metabolic dysfunction, cancer, fibrosis, and neurodevelopment.
• To highlight CILP2's potential as a biomarker and therapeutic target.

Main Methods:

• Literature review and synthesis of existing research.
• Analysis of genomic studies linking the NCAN-CILP2 locus to cardiovascular risk.
• Functional studies investigating CILP2's role in metabolic pathways, fibrosis, neurodevelopment, and cancer.

Main Results:

• CILP2 is upregulated by metabolic stressors like high glucose and oxidized LDL (oxLDL).
• CILP2 impairs glucose metabolism and mitochondrial function, contributing to dyslipidemia, diabetes, and sarcopenia.
• CILP2 promotes fibrosis and neurogenesis and acts as an oncoprotein in various cancers, driving proliferation and metastasis.
• Serum CILP2 levels correlate with disease severity and poor prognosis.

Conclusions:

• CILP2 is a critical mediator in metabolic diseases, cancer, and fibrosis.
• CILP2's involvement in diverse pathologies underscores its significance in human health.
• CILP2 represents a promising biomarker and therapeutic target for a range of diseases.