PALMD, encoding palmdelphin, is involved in multiple biological processes. It plays a role in myoblast differentiation, and is associated with pathways like glycolysis, NF-κB-mediated inflammation, extracellular matrix remodeling, and is important for cardiac development and remodeling [1,2,3]. Genetic models, such as gene knockout mouse models, are valuable for studying PALMD's functions.

In gene knockout studies, PALMD haploinsufficiency in mice aggravated subtotal nephrectomy-induced vascular calcification, disturbing extracellular matrix synthesis and degradation in aortas [3]. Palmd -deficient mice of advanced age showed features of calcific aortic valve disease, like increased aortic valve peak velocity and thickened leaflets [4]. Germline and cardiomyocyte -specific Palmd knockout mice exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment, with PALMD ablation perturbing transverse tubule-sarcoplasmic reticulum ultrastructures [5,6].

In conclusion, PALMD is essential for normal physiological functions, especially in cardiovascular-related processes. Studies using KO mouse models have revealed its significant roles in vascular and aortic valve calcification, as well as in protecting against isoproterenol-induced cardiac injury. These findings highlight PALMD as a potential therapeutic target for diseases such as calcific aortic valve stenosis and vascular calcification.