PCSK9 at the intersection of lipid metabolism, immunometabolism, and psychiatric disorders: A narrative review.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a central regulator of lipid metabolism and a well-established determinant of cardiovascular risk. In addition to its hepatic role in cholesterol homeostasis, PCSK9 is increasingly linked to immunometabolic processes that overlap with biological alterations commonly observed in psychiatric disorders, including dyslipidemia, insulin resistance, and low-grade systemic and neuroinflammation. This narrative review synthesizes experimental, genetic, and clinical evidence on lipid metabolism and PCSK9-related pathways in psychiatric disorders. Disorder-specific patterns of peripheral lipid abnormalities are reviewed alongside evidence for altered central lipid composition and cholesterol turnover in major psychiatric and neuropsychiatric conditions. Available data on PCSK9 expression and regulation within the central nervous system (CNS) are summarized, together with studies examining circulating PCSK9 levels in relation to metabolic burden, inflammation, and psychiatric symptomatology. Overall, the literature positions PCSK9 within interconnected metabolic and inflammatory pathways associated with psychiatric vulnerability, primarily as a peripheral marker. Although PCSK9 is implicated in neuroinflammation and may intersect with pathways relevant to brain insulin resistance, its role within the CNS remains incompletely characterized in relation to psychiatric disorders, highlighting an important area for future mechanistic and translational research.