TRIM54 (tripartite motif containing 54) is a muscle-specific E3 ubiquitin ligase that plays critical roles in sarcomere formation and protein homeostasis. As part of the muscle-specific RING finger (MuRF) family, TRIM54 localizes to sarcomeric M-bands and Z-discs where it functions as a microtubule-associated protein involved in stabilizing microtubules during myotube formation 1. The protein exerts its regulatory functions through K63-linked ubiquitination of target proteins, including filamin C degradation in gastric cancer progression 2 and FSP1 degradation in sorafenib-induced ferroptosis 3. TRIM54 also stabilizes YOD1 protein in tendon-derived stem cells, reducing inflammation and apoptosis 4. Disease-wise, mutations in TRIM54 combined with TRIM63 mutations cause a novel protein aggregate myopathy characterized by proximal muscle weakness, hypertrophic cardiomyopathy, and aberrant protein inclusions lacking thin filaments and Z-discs 1. Additionally, TRIM54 serves as a circulating biomarker for acute myocardial infarction, with plasma levels significantly elevated in AMI patients 5. The gene shows genetic associations with both gestational diabetes mellitus and type 2 diabetes, potentially influencing energy balance signaling and skeletal muscle metabolism 6.