Palladin (PALLD) is an actin-associated protein that belongs to the PALLD/myopalladin (MYPN)/myotilin family. It plays essential roles in multiple biological processes, mainly through its involvement in regulating the actin cytoskeleton. It has been associated with pathways related to cell differentiation, phagocytosis, and muscle-related functions, which are crucial for normal physiological activities and tissue development [2,3,4]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, have been valuable for studying PALLD's functions.

In a megakaryocyte/platelet-specific KO mouse model, PALLD deficiency led to thrombocytopenia due to diminished platelet biogenesis, impaired proplatelet formation, and polyploidization in megakaryocytes. Mechanistically, PALLD binds to STAT3, and its absence attenuates STAT3 Y705 phosphorylation and impedes STAT3 nuclear translocation [1]. In adult cardiomyocyte-specific inducible CKO mice, ablation of PALLD caused progressive cardiac dilation, systolic dysfunction, reduced cardiomyocyte contractility, intercalated disc abnormalities, and fibrosis, indicating its essential role in normal cardiac function [3].

In conclusion, PALLD is crucial for processes like megakaryocyte differentiation and normal cardiac function. Studies using KO and CKO mouse models have revealed its significance in thrombocytopenia and cardiomyopathy, respectively. These findings enhance our understanding of the biological functions of PALLD and provide potential targets for treating related diseases.