TRIM55 is an E3 ubiquitin ligase that functions as a multifaceted regulator of cardiac and skeletal muscle physiology, with emerging roles in immune signaling and cancer suppression. In cardiac development, TRIM55 regulates cardiomyocyte size and contractility through ubiquitin-mediated protein degradation pathways 1. The protein mediates non-canonical NF-κB signaling by promoting NFKB2 ubiquitination, influencing immune responses 2. TRIM55 stability is modulated by SUMO-3-dependent mechanisms; SIM motifs regulate its polyubiquitination, subcellular localization, and catalytic activity 3. Clinically, TRIM55 acts as a tumor suppressor across multiple cancer types. In colorectal cancer, TRIM55 inhibits progression by promoting c-Myc protein degradation, suppressing cell growth and migration 4. Similarly, in hepatocellular carcinoma and lung adenocarcinoma, TRIM55 overexpression reduces migration and invasion through enhanced degradation of metastasis-associated transcription factors (MMP2 and Snail1) 56. Genetic variants in TRIM55, such as the E140K substitution, impair cardiomyocyte viability and cardiac contractility, linking TRIM55 polymorphisms to heart failure susceptibility 17. The gene's downregulation in disease states and tumor-suppressive functions identify TRIM55 as a promising therapeutic target for cardiac and malignant conditions.