Background <p>Vascular calcification is associated with atherosclerosis, plaque destabilization and related cardiovascular risk/mortality. A key cell type involved in vascular calcification is the vascular smooth muscle cell (VSMC). Although several studies have reported the role of non-coding RNAs in regulating vascular calcification, the expressions and functions of certain circular RNAs in vascular calcification have not yet been fully explored. This study aimed to identify the differentially expressed circRNAs involved in the calcification of VSMCs and explore the regulatory function and molecular mechanism of certain circRNA.</p> Methods and results <p>High-throughput sequencing and qRT‒PCR revealed that circ-GALK2 (hsa_circ_0008488), a circular RNA generated from the GALK2 gene, was prominently upregulated in calcified VSMCs. Gain-of-function studies indicated that the overexpression of circ-GALK2 promoted VSMC calcification <i>in vitro</i>. We investigated the mechanism of circ-GALK2 as a microRNA sponge and noted that miR-134-3p and CD36 are downstream targets of circ-GALK2. The overexpression of circ-GALK2 promoted VSMC calcification by sponging miR-134-3p and increasing CD36 expression. The above effects were neutralized by the overexpression of miR-134-3p. We also confirmed the expression of the circ-Galk2/miR-134-3p/Cd36 axis in a mouse aortic calcification model. In addition, we investigated the relationship between plasma circ-GALK2 expression and human aortic calcification.</p> Conclusions <p>The current study elucidates the unique expression and critical function of the circ-GALK2/miR-134-3p/CD36 axis in vascular smooth muscle calcification, potentially offering significant insights for developing strategies to mitigate the progression of vascular calcification disease. Furthermore, this axis is anticipated to serve as a biomarker and a prospective therapeutic target for vascular calcification.</p> Graphical Abstract <p></p>