MYPN (myopalladin) is a striated muscle-specific Z-disc protein that functions as a structural and signaling molecule in the sarcomere. It serves as a tether anchoring nebulin (skeletal muscle) or nebulette (cardiac muscle) to α-actinin at the Z-line 1. Beyond its structural role, MYPN regulates muscle growth through modulation of the serum response factor (SRF) pathway by controlling actin dynamics and interacting with MRTF-A, a SRF cofactor 2. MYPN also localizes to the nucleus and intercalated discs, where it participates in gene expression regulation and cell-cell adhesion 1. Mutations in MYPN cause diverse cardiomyopathies through distinct mechanisms. Heterozygous missense variants (e.g., Y20C) disrupt nuclear translocation and CARP binding, leading to hypertrophic or dilated cardiomyopathy via abnormal intercalated disc assembly 1. Nonsense mutations (e.g., Q529X) impair myofibrillogenesis, resulting in restrictive cardiomyopathy 1. Homozygous loss-of-function mutations cause skeletal myopathies including cap myopathy, nemaline myopathy, and congenital myopathy, associated with reduced myofiber cross-sectional area and impaired Z-line integrity during aging and exercise stress 2. MYPN variants are also implicated in atrial fibrillation susceptibility 3. These findings underscore MYPN's critical role in both cardiac and skeletal muscle homeostasis and adaptation.