CSRP3 (cysteine and glycine-rich protein 3), also known as muscle LIM protein (MLP), is a sarcomere-associated protein essential for cardiac muscle organization and function. Functionally, CSRP3 plays a critical role in early sarcomere organization and Z-disc assembly, with proposed mechanisms involving regulation of actin dynamics through modulation of cofilin-2 (CFL2)-mediated F-actin depolymerization 1. CSRP3 also functions as a cardiac-derived endocrine factor that transits plasma after cardiac injury and undergoes megalin-dependent endocytosis in renal proximal tubules, contributing to post-cardiac injury kidney fibrosis 2. Disease relevance is substantial: CSRP3 mutations cause both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) 13. CSRP3 was most recently classified with definitive evidence for semidominant HCM inheritance 45. CSRP3 deficiency in animal models produces excessive cardiac trabeculation and impairs heart regeneration by disrupting cardiomyocyte dedifferentiation, sarcomere reassembly, and proliferation 3. Intermediate-effect variants in CSRP3 contribute to ~4.8% of HCM genetic burden and modify disease severity when combined with monogenic variants 6. Clinically, CSRP3 testing should be included in HCM genetic panels given its definitive disease association, and variant interpretation should account for both rare pathogenic variants and intermediate-frequency missense variants affecting disease expression and outcomes.