Palmd, encoding palmdelphin, is a protein involved in myoblast differentiation. It has been linked to pathways like glycolysis, NF-κB-mediated inflammation, and is associated with cardiac development, remodeling, and extracellular matrix regulation [1,2]. It is also thought to play a role in plasma membrane dynamics [6].

In calcific aortic valve disease (CAVD), reduced Palmd expression is associated with increased risk. Palmd-deficient mice show features of CAVD such as increased aortic valve peak velocity and thickened leaflets. In these mice, loss of Palmd impairs TNFAIP3-dependent deubiquitinating activity in valvular endothelial cells, promoting NF-κB activation and aortic valvular remodeling [3]. In vascular smooth muscle cells, Palmd haploinsufficiency (Palmd+/-) aggravates subtotal nephrectomy-induced vascular calcification, disturbing extracellular matrix synthesis and degradation [2]. In the context of isoproterenol-induced cardiac injury, germline and cardiomyocyte-specific Palmd knockout mice exhibit compromised cardiac hypertrophy and aggravated injury, while cardiomyocyte-specific Palmd overexpression mitigates the injury. Palmd ablation also perturbs transverse tubule-sarcoplasmic reticulum ultrastructures [5,7]. In uveal melanoma, low levels of Palmd contribute to metastasis as it promotes cell invasion and migration [4].

In conclusion, Palmd plays essential roles in multiple biological processes, especially in cardiovascular-related functions and diseases. Gene knockout models, such as Palmd-deficient and haploinsufficient mice, have significantly contributed to understanding its role in calcific aortic valve stenosis, vascular calcification, aortic valvular remodeling, and myocardial injury protection. It also has implications in uveal melanoma metastasis. These findings suggest Palmd could be a potential therapeutic target for these diseases.