The study investigates the role of circular antisense non-coding RNA in the INK4 locus (*circANRIL*) in human atherosclerosis. *circANRIL* is expressed at a locus associated with cardiovascular disease and is found to modulate ribosomal RNA (rRNA) maturation and atherogenesis. *circANRIL* binds to pescadillo homologue 1 (PES1), an essential component of the 60S-preribosomal assembly complex, impairing pre-rRNA processing and ribosome biogenesis in vascular smooth muscle cells and macrophages. This results in nucleolar stress and p53 activation, leading to apoptosis and inhibited proliferation, which are key cellular functions in atherosclerosis. The study identifies *circANRIL* as a regulator of ribosome biogenesis and a potential therapeutic target for atherosclerosis, highlighting the importance of circular RNAs in human disease.The study investigates the role of circular antisense non-coding RNA in the INK4 locus (*circANRIL*) in human atherosclerosis. *circANRIL* is expressed at a locus associated with cardiovascular disease and is found to modulate ribosomal RNA (rRNA) maturation and atherogenesis. *circANRIL* binds to pescadillo homologue 1 (PES1), an essential component of the 60S-preribosomal assembly complex, impairing pre-rRNA processing and ribosome biogenesis in vascular smooth muscle cells and macrophages. This results in nucleolar stress and p53 activation, leading to apoptosis and inhibited proliferation, which are key cellular functions in atherosclerosis. The study identifies *circANRIL* as a regulator of ribosome biogenesis and a potential therapeutic target for atherosclerosis, highlighting the importance of circular RNAs in human disease.