The article provides an overview of the ubiquitin-proteasome pathway, highlighting its role in protein degradation and cellular processes. The discovery of this pathway has revolutionized our understanding of intracellular protein turnover, revealing it to be a highly complex and tightly regulated process involving multiple enzymes and specific substrates. The pathway is involved in the regulation of cell cycle, differentiation, stress response, morphogenesis, immune and inflammatory responses, DNA repair, and apoptosis. The degradation process involves two main steps: ubiquitination, where multiple ubiquitin molecules are covalently attached to the target protein, and proteolysis, where the tagged protein is degraded by the 26S proteasome. The article discusses the enzymes involved in these steps, including E1, E2, and E3 ligases, and the structural motifs that target proteins for ubiquitination. It also explores the involvement of the ubiquitin system in various diseases, both inherited and acquired, such as malignancies, genetic disorders, immune and inflammatory responses, neurodegenerative diseases, and muscle wasting. The article concludes by emphasizing the importance of understanding the ubiquitin system in disease pathogenesis and therapeutic intervention.The article provides an overview of the ubiquitin-proteasome pathway, highlighting its role in protein degradation and cellular processes. The discovery of this pathway has revolutionized our understanding of intracellular protein turnover, revealing it to be a highly complex and tightly regulated process involving multiple enzymes and specific substrates. The pathway is involved in the regulation of cell cycle, differentiation, stress response, morphogenesis, immune and inflammatory responses, DNA repair, and apoptosis. The degradation process involves two main steps: ubiquitination, where multiple ubiquitin molecules are covalently attached to the target protein, and proteolysis, where the tagged protein is degraded by the 26S proteasome. The article discusses the enzymes involved in these steps, including E1, E2, and E3 ligases, and the structural motifs that target proteins for ubiquitination. It also explores the involvement of the ubiquitin system in various diseases, both inherited and acquired, such as malignancies, genetic disorders, immune and inflammatory responses, neurodegenerative diseases, and muscle wasting. The article concludes by emphasizing the importance of understanding the ubiquitin system in disease pathogenesis and therapeutic intervention.