Filamin C, encoded by the FLNC gene, is a major actin-binding protein essential for maintaining key muscle cell functions, especially for the structural integrity and cell signaling of the sarcomere, and it participates in sarcomere stability maintenance [1,4]. It is also involved in regulating muscle cell proliferation, migration, and differentiation, and has a direct link with the activity of TEAD-YAP/TAZ signaling [3].

FLNC variants are associated with various cardiac and muscular phenotypes. Truncating variants are often linked to dilated cardiomyopathy (DCM) and cardiac arrhythmias, likely due to haploinsufficiency. These truncating mutations can cause an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies with a high risk of sudden cardiac death [1,2]. Missense variants, on the other hand, are predominantly found in hypertrophic cardiomyopathy (HCM) and myofibrillar myopathy (MFM), where they may interfere with protein dimerization and folding, leading to aggregate formation detrimental to muscle function [1]. In a study of a murine myoblast cell line with stably suppressed Flnc expression, FLNC-deficient myoblasts showed a higher proliferation rate, impaired cell migration, and an inability to complete myogenic differentiation, along with alterations in myogenic factor transcriptional dynamics and deregulation of the Hippo signaling pathway [3].

In conclusion, FLNC is crucial for normal muscle cell function. Studies, including those using models with suppressed Flnc expression, have revealed its role in multiple muscle-related biological processes and its significant association with cardiomyopathies. Understanding FLNC's cellular biology and molecular regulation can potentially lead to new therapies for FLNC-related cardiomyopathy [4].