Nuclear lamins, the unique type 5 intermediate filaments of the nucleus, form a structural network beneath the nuclear envelope. Through their strategic localization, they interact with numerous partners and regulate a wide range of biochemical and biophysical processes. In load-bearing tissues such as the heart, nuclear lamins are crucial for maintaining mechanical integrity and genome stability during cardiac contraction. By associating with chromatin through lamina-associated domains, they play a fundamental role in genome organization and gene expression. Disruption of the nuclear lamin meshwork in CardioLaminopathy leads to chromatin remodeling and dysregulated gene expression. Although the precise cellular and molecular mechanisms driving CardioLaminopathy remain incompletely understood, alterations in genome organization are emerging as key contributors to disease pathogenesis and progression.