ApoJ

ApoJ, also known as apolipoprotein J or clusterin, is a secreted glycoprotein encoded by the CLU gene in humans. It is a member of the apolipoprotein family and is widely expressed, with notable levels in liver, brain, kidney, and other tissues. The mature secreted form is a heterodimer of alpha and beta chains linked by disulfide bonds, and it is commonly found in plasma, cerebrospinal fluid, urine, and extracellular matrix as part of lipoprotein-like particles.

In addition to the secreted form, alternative splicing produces a cytoplasmic/nuclear isoform (nCLU) that is not secreted and can participate in pro-apoptotic pathways under cellular stress. The secreted clusterin (sCLU) is generally described as an extracellular chaperone, helping to prevent aggregation of misfolded proteins and to aid in proteostasis.

ApoJ performs multiple functions, including lipid transport, modulation of inflammation and immune responses, and regulation of the complement system. As an extracellular chaperone, it binds misfolded or aggregating proteins, including amyloid-β, and can influence their clearance and deposition. It also participates in cell survival signaling and can influence apoptotic pathways in a context-dependent manner depending on the isoform and environment.

Clinical relevance has grown around ApoJ due to its association with aging and neurodegenerative diseases. Genetic variants in CLU have been linked to altered risk of late-onset Alzheimer’s disease in genome-wide association studies, and clusterin levels in plasma or cerebrospinal fluid are studied as potential biomarkers in neurological disorders, cancer, and vascular diseases. Ongoing research explores its mechanistic roles in protein clearance, immune regulation, and cellular stress responses, as well as its potential as a therapeutic target.