PALMD, encoding palmdelphin, is involved in multiple biological processes. It plays a role in myoblast differentiation and is associated with pathways such as those related to cardiac development, remodeling, glycolysis, NF-κB-mediated inflammation, and extracellular matrix synthesis and degradation. Its function in maintaining normal cellular activities in various tissues, including the heart, aorta, and neurons, highlights its biological importance. Genetic models, such as gene knockout mice, are valuable tools for studying PALMD's function [1,2,3,4,5,6].

Reduced PALMD expression is linked to diseases like calcific aortic valve stenosis (CAVS) and vascular calcification. In Palmd haploinsufficient mice, there is aggravated subtotal nephrectomy-induced vascular calcification, along with ECM dysregulation in vascular smooth muscle cells [3]. In Palmd-deficient mice of advanced age, there are features of calcific aortic valve disease, including increased aortic valve peak velocity and thickened leaflets [4]. Also, germline and cardiomyocyte-specific Palmd knockout mice exhibit compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment [6,7].

In conclusion, PALMD is crucial for maintaining normal physiological functions in the cardiovascular system and other tissues. The use of Palmd knockout mouse models has significantly contributed to understanding its role in diseases such as CAVS, vascular calcification, and cardiac injury. These findings suggest PALMD could be a potential therapeutic target for these diseases [1,3,4,6].

References:

1. Bossé, Yohan, Mathieu, Patrick, Thériault, Sébastien. . PALMD as a novel target for calcific aortic valve stenosis. In Current opinion in cardiology, 34, 105-111. doi:10.1097/HCO.0000000000000605. https://pubmed.ncbi.nlm.nih.gov/30608251/

2. Wang, Siying, Yu, Hongjiao, Gao, Jun, Jiang, Lei, Zhu, Dongxing. 2022. PALMD regulates aortic valve calcification via altered glycolysis and NF-κB-mediated inflammation. In The Journal of biological chemistry, 298, 101887. doi:10.1016/j.jbc.2022.101887. https://pubmed.ncbi.nlm.nih.gov/35367413/

3. Zhang, Jichao, Yang, Zhao, Zhang, Congcong, You, Bin, Han, Yingchun. 2024. PALMD haploinsufficiency aggravates extracellular matrix remodeling in vascular smooth muscle cells and promotes calcification. In American journal of physiology. Cell physiology, 327, C1012-C1022. doi:10.1152/ajpcell.00217.2024. https://pubmed.ncbi.nlm.nih.gov/39246140/

4. Han, Yingchun, Zhang, Jichao, Yang, Zhao, Liu, Jinghua, Du, Jie. 2023. Palmdelphin Deficiency Evokes NF-κB Signaling in Valvular Endothelial Cells and Aggravates Aortic Valvular Remodeling. In JACC. Basic to translational science, 8, 1457-1472. doi:10.1016/j.jacbts.2023.06.004. https://pubmed.ncbi.nlm.nih.gov/38093741/

5. Srivastava, Yogesh, Donta, Maxsam, Mireles, Lydia L, Waxham, M Neal, McCrea, Pierre D. 2023. Role of a Pdlim5:PalmD complex in directing dendrite morphology. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.08.22.553334. https://pubmed.ncbi.nlm.nih.gov/37662414/

6. Guo, Cong-Ting, Jardin, Blake D, Lin, Jun-Sen, Pu, William T, Guo, Yu-Xuan. 2024. In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-disc-associated mitigator of isoproterenol-induced cardiac injury. In Acta pharmacologica Sinica, 45, 2540-2552. doi:10.1038/s41401-024-01348-y. https://pubmed.ncbi.nlm.nih.gov/39043970/

7. Guo, Congting, Jardin, Blake D, Lin, Junsen, Pu, William T, Guo, Yuxuan. 2023. In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-line-associated mitigator of isoproterenol-induced cardiac injury. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.12.06.570334. https://pubmed.ncbi.nlm.nih.gov/38106146/