The ubiquitin-proteasome system (UPS) involves numerous components and its overactivation characterized by a muscle-specific increase of type E3 ubiquitin ligases, atrogin-1 (Muscle Atrophy F-box, MAFbx), and MuRF-1 (Muscle-specific RING-finger protein 1) constitutes a major catabolic mechanism resulting in sarcopenia [118,119]. The gene discussed is TRIM63; the disease is sarcopenia.