MYOZ3 (myozenin 3) is a Z-disc protein that functions as an intracellular binding protein linking sarcomeric Z-line components including alpha-actinin, gamma-filamin, TCAP/telethonin, and LDB3/ZASP, while localizing calcineurin signaling to the sarcomere. In chicken embryonic fibroblasts and myoblasts, MYOZ3 overexpression significantly upregulated cell proliferation rates and fast muscle-specific gene expression, with pathway analysis suggesting regulation of muscle fiber development through the PPAR signaling pathway 1. MYOZ3 plays an important role in myofibrillogenesis and modulation of calcineurin signaling. Clinically, rare loss-of-function variants in MYOZ3 are associated with sarcopenic obesity susceptibility (OR = 25.49, p = 1.41 × 10⁻⁷) 2, suggesting a protective role in maintaining muscle mass. Additionally, MYOZ3 was identified as a shared differentially expressed protein in skeletal muscle across multiple cancer cachexia models, indicating potential involvement in muscle wasting pathways 3. However, MYOZ3 variants (rs1142544043) were not associated with type 2 polysaccharide storage myopathy or myofibrillar myopathy in Quarter Horses, limiting their diagnostic utility in equine muscle disease 4.