KBTBD13 is a striated muscle-expressed protein that functions as a substrate-specific adapter of the BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex 1. The protein localizes to the sarcomere where it directly binds actin, a major thin filament constituent, modulating muscle kinetics and relaxation 12. Mutations in KBTBD13, particularly the Dutch founder variant p.Arg408Cys, cause nemaline myopathy type 6 (NEM6), an autosomal-dominant disorder characterized by nemaline rods and core lesions in skeletal myofibers 3. Disease-associated mutations alter KBTBD13's effects on actin structure, increasing thin-filament stiffness and impairing muscle-relaxation kinetics, which leads to muscle weakness and slow relaxation compromising daily activities 21. Beyond skeletal muscle involvement, KBTBD13 variants are associated with cardiac dysfunction; approximately 29% of NEM6 patients develop reduced left ventricular ejection fraction, with some experiencing sudden cardiac death 4. Mouse models show that p.R408C variants cause mild diastolic dysfunction while KBTBD13 deficiency produces systolic dysfunction 4. These findings indicate KBTBD13 should be included in cardiomyopathy gene panels and that NEM6 patients require cardiac evaluation 4.