Abstract Body: LMNA mutations cause a heterogeneous spectrum of disorders, including lipodystrophy, progeria, skeletal myopathies, and cardiomyopathies. Cardiac laminopathies frequently present with arrhythmia as the initial manifestation and are classified as arrhythmogenic cardiomyopathy (ACM). Although Lamin A/C is integral to nuclear envelope integrity, how pathogenic LMNA variants disrupt Lamin A/C structure in cardiomyocytes (CMs) and cardiac fibroblasts (CFs) to produce a distinct electrophysiologic phenotype remains unclear. Notably, ACM-associated LMNA^+/E203K has not been physiologically characterized in vitro. We generated LMNA^+/E203K heterozygous DT19-9-11T iPSCs by CRISPR/Cas9 genome editing. iPSC-derived CMs and CFs were differentiated and co-cultured to form cardiac microtissues on PDMS substrates with stiffnesses representative of healthy (10 kPa) and diseased (50 kPa) myocardium to introduce changes in the mechanical environment. Optical voltage and calcium mapping revealed a striking arrhythmogenic phenotype in LMNA^+/E203K microtissues characterized by calcium transient alternans and 2:1 conduction block during dynamic pacing. Spontaneous activation sites were spatially unstable and demonstrated post-pacing rate acceleration that was enhanced on 50 kPa substrates, consistent with abnormal automaticity and impaired rate adaptation. Compared with controls, LMNA^+/E203K tissues exhibited prolonged action potential duration during 1.5 Hz pacing at 10 kPa stiffness, with no differences at 50 kPa and displayed increased Ca²⁺ transient duration only on 50 kPa substrates. Confocal imaging of LMNA^+/E203K iPSC-CMs and CFs showed decreased nuclear circularity and cytoskeletal disorganization on 10 kPa substrates, which was further exacerbated on the 50 kPa compared to control. Collectively, these findings demonstrate that ACM-associated LMNA^+/E203K mutation produces a highly arrhythmogenic cardiac microtissue phenotype characterized by abnormal automaticity and prolonged refractoriness. These electrophysiologic defects are accompanied by impaired nuclear mechanoadaptation in both CMs and CFs with stiffness-dependent cytoskeletal disorganization, indicating disrupted nuclear-cytoskeletal integration. Together, these results identify defective electromechanical coupling as a key mechanism in LMNA-associated ACM and establish a translational platform to study how nuclear lamina alterations in CMs and CFs drive electrophysiologic dysfunction.