2019). Abundantly and differentially expressed piRNAs are discovered in cardiomyocytes during cardiac hypertrophy (Rajan et al. 2016). DQ726659/PIWI‐like protein 4 (PIWIL4) complex participates in the regulation of cardiac hypertrophy (Gao et al. 2020). piR‐000691 aggravates fibroblast activation by targeting apelin (Chen et al. 2024). Dysregulated serum‐originated sEV‐derived piRNAs are identified in patients with HF (Yang et al. 2018), although their functional relevance to cardiac remodelling has not yet been directly addressed. The gene discussed is PIWIL4; the disease is cardiac hypertrophy.