FHOD3 (formin homology 2 domain containing 3) is an actin-organizing protein that plays a crucial role in cardiomyocyte sarcomere organization and cardiac muscle function 1. The protein contains conserved FHDHN, FH1, FH2, and FHDHC domains and exists in multiple isoforms due to alternative splicing 2. FHOD3 functions in actin filament polymerization and organization, particularly in cardiac myofibrils, where it is essential for proper sarcomere assembly and maintenance 1. Loss of FHOD3 function leads to severe sarcomere disorganization, impaired calcium handling, compromised mitochondrial function, and reduced contractility in cardiomyocytes 1. The protein also appears to regulate CaMKII signaling pathways, with FHOD3 deficiency triggering CaMKII phosphorylation and activation 1. Mutations in FHOD3 are definitively associated with hypertrophic cardiomyopathy (HCM), with the gene recently receiving definitive classification for HCM causation by the ClinGen expert panel 34. Additionally, intermediate-effect variants in FHOD3 contribute to HCM genetic burden and can modify disease severity, particularly when combined with other pathogenic variants 5. These findings establish FHOD3 as a critical non-sarcomeric gene in cardiac muscle function and inherited cardiomyopathy.