Palladin (PALLD) is an actin-associated protein that belongs to the PALLD/myopalladin (MYPN)/myotilin family of actin-associated immunoglobulin-containing proteins in the sarcomeric Z-line. It is ubiquitously expressed in several isoforms. PALLD plays essential roles in multiple biological processes, such as regulating actin polymerization and depolymerization, which is involved in pathways like phagocytosis, megakaryocyte differentiation, and skeletal muscle satellite cell differentiation [2,1,4]. Genetic models, like knockout mouse models, have been crucial for studying its functions.

In megakaryocyte/platelet-specific Palld knockout mice, thrombocytopenia occurred due to reduced platelet biogenesis. PALLD deficiency in megakaryocytes led to impaired proplatelet formation and polyploidization, weakening their differentiation for platelet production. Mechanistically, PALLD binds to STAT3, and its absence attenuates STAT3 Y705 phosphorylation and nuclear translocation [1]. In adult cardiomyocyte-specific inducible PALLD knockout mice, ablation caused progressive cardiac dilation, systolic dysfunction, reduced cardiomyocyte contractility, intercalated disc abnormalities, and fibrosis, demonstrating its importance for normal cardiac function [3].

In conclusion, PALLD is crucial for normal cellular functions in processes like megakaryocyte differentiation and cardiac function. The study of PALLD through KO/CKO mouse models has provided insights into its role in thrombocytopenia and heart-related diseases, highlighting its potential as a therapeutic target in these disease areas.